Chemical and physicochemical properties of LDL and Lp(a)
Lipoprotein (a) [Lp(a)], first described in 1963 is an inherited cholesterol-rich particle found in a density range of 1.055-1.120 g/ml. The suggestion that Lp(a) might be a risk factor for cardiovascular diseases was first made by Dahlen et al.  who found out that individuals with angina pectoris exhibit an “extra pre-β-band” in lipid electrophoresis. In whites the concentration of Lp(a) in plasma varies from undetectable up to 200 mg/dl in different individuals but seems to be rather constant in the same person . Chemical and physicochemical properties of Lp(a) in comparison with LDL are summarized in table 1.
Plasma Lp(a) concentrations above 30 mg/dl, as measured in about 20 percent of white people, are associated with an approx. two-fold relative risk of coronary atherosclerosis  rising to the range of five-fold when LDL and Lp(a) are both elevated . Interestingly, blacks with high levels of Lp(a) do not experience greatly increased atherosclerotic progression and mortality. In those cases it is assumed that the atherogenicity of Lp(a) must be decreased or counterbalanced by other factors .
Till now the site and mechanism of Lp(a) synthesis are quite unclear. Measurements of serum Lp(a) levels of patients suffering from liver disease or from cholestasis who showed significantly lower concentrations than healthy controls gave indications that Lp(a) might be synthesized by the liver . On the other hand there are studies which suggest that apo-a is associated with the postprandial d < 1.006 lipoproteins induced by fat feeding  but it is not yet clear however whether apo-a determined in this fraction is really of intestinal origin or whether it originates from free apo-a in serum which might bind to freshly secreted chylomicrons . Because of the chemical similarities between Lp(a) and LDL it is possible that Lp(a) is formed during the metabolic catabolism of chylomicrons, VLDL or LDL. As Lp(a) levels stay nearly constant within one individual and as lipid-rich diet as well as fasting have no influence on Lp(a) concentrations it is assumed that Lp(a) exhibits a metabolic behaviour completely different from other apo-B containing lipoproteins. Turnover studies in vivo performed with labelled VLDL confirmed these assumptions. Nearly all the activity of labelled VLDL could be detected in LDL whereas only trace amounts could be found in Lp(a)  confirming the hypothesis that unlike LDL, Lp(a) probably has no triglyceride-rich lipoproteins as precursors but seems to be secreted directly by the liver . On the other hand the site of catabolism of Lp(a) in humans is unknown so far although the kidney is favourized to be implicated .
Despite extensive work on Lp(a) its possible physiological function remains unclear till now.
|Hydr. Density [g/ml]||1.034||1.085|
|Mol. Wt. [x 106]||2.4||5.5|
|Chem. Composition [%]|
2. Structural arrangement and catabolism of Lp(a)
The major protein component of this LDL-like particle is apolipoprotein B (apo-B-100) which carries an additional protein called apolipoprotein-a [apo-a] linked to apo-B-100 via disulphide bridges (Fig.1) the lipid moiety however being almost indistinguishable from that of LDL . Human apo-a itself consists of multiple so-called kringle repeats, sequences consisting of 80-90 amino acids arranged in a tripleloop tertiary structure and tandemly arrayed resembling kringles IV and V of plasminogen and a protease domain . Copy number variants in the LPA gene on chromosome 6 coding for apo-a are responsible for a variation of plasma Lp(a) levels of up to 1000-fold among individuals. The most influential is the kringle IV-2 size polymorphism  while kringle IV types 1 and 3-10 as well as kringle V occur only once in Lp(a) . The number of kringle IV type 2 structure repeats results in a large number of different sized isoforms of apo-a and correlates inversely with the plasma concentration of Lp(a) . Although the exact mechanism responsible for this inverse correlation has not been elucidated so far an isoform dependent retention and degradation in the endoplasmatic reticulum has been implicated .
Contradictory results have been reported about the clearance of Lp(a) and till now it remains unclear whether Lp(a) binds to the B/E receptor via apo-B like LDL or whether it is catabolised independently of the LDL-receptor mediated pathway. Whereas in one study using fibroblasts from normal subjects and from subjects with autosomal dominant hypercholesterolemia the conclusion was reached that Lp(a) enters fibroblasts independently of the LDL-receptor  others concluded that Lp(a) is also bound to the LDL-receptor, internalized and degraded but with a degradation capacity of only 25% of that of LDL . Binding studies of native and reduced Lp(a) with different monoclonal antibodies against apolipoprotein B revealed that there was no antibody that failed to react with native Lp(a) but some of the antibodies recognized apoB of Lp(a) to a lesser degree than that of LDL. This favoured the idea that certain regions on apo-B of Lp(a) could be different from those on LDL and led to the assumption that certain domains close to the binding domain of Lp(a) to the B/E-receptor could be covered by apo-a or that apo-a causes conformational changes in the binding region of apo-B thereby constricting the binding of Lp(a) to the LDL-receptor  being in agreement with the fact that normal unreduced Lp(a) seemed to be taken up by fibroblasts through B/E-receptor-mediated endocytosis but showed poorer specificity for the receptor than LDL .
3. Free apolipoprotein-a in human serum
In the beginning of “Lp(a)-research” this lipoprotein was believed to represent a genetically polymorphic form of LDL . According to this assumption apo-a should distribute uniformly between all apo-B-containing lipoproteins. Investigation of this problem in more detail revealed that Lp(a) forms a particular lipoprotein class found primarily in the HDL-2 density region  but can also be detected in LDL class (d = 1.019-1.063 g/ml)  and even in chylomicrons induced by fat feeding . The fact however that a portion of the Lp(a)-specific antigen can be found in the d > 1.21 g/ml lipoprotein free bottom fraction after ultracentrifugation of plasma  led to further investigation of this phenomenon. Apo-a is virtually absent in the VLDL fraction (d < 1.006 g/ml) of freshly drawn fasting human sera while 95% of total Lp(a) can be obtained in the d > 1.006 g/ml bottom fraction. Approximately 5% of the total serum Lp(a) are found in the d > 1.125 g/ml bottom fraction after ultracentrifugation as well as with polyanionic precipitation agents irrespective of the Lp(a) concentration in serum . Due to the lack of Sudan Black staining this bottom Lp(a) is considered as a lipid free “apo-a protein” raising the question whether or not free apo-a can reassociate with LDL to form “native Lp(a)”.
4. Lp(a) and platelet aggregation
One of the physiological roles of platelets involves binding to subendothelial tissue after vascular injury . The adherence of platelets to the exposed connective tissue, preferably collagen, leads to aggregation followed by the release of ADP, 5-hydroxytryptamine and Ca2+ from their dense granules, causing passing platelets to adhere to the primary clot .
There is little doubt that lipoproteins interfere with platelets in vivo being reflected by the fact that platelets from hyperlipoproteinemic patients are hyperreactive . This is confirmed by the fact that incubation of platelets with physiological concentrations of atherogenic apoB-containing lipoproteins such as LDL or VLDL results in enhanced platelet aggregability  while antiatherogenic lipoproteins such as HDL exert the opposite effect . Concerning Lp(a) it is generally accepted that elevated plasma concentrations of this lipoprotein are connected with premature atherosclerosis  but much uncertainty remains about the influence of Lp(a) on platelet activation, a phenomenon that is believed to be involved not only in long-term processes of plaque formation but also in acute events such as stroke and myocardial infarction . Moreover a two-fold increase in the risk of coronary heart disease (CHD) and ischaemic stroke could be demonstrated especially in subjects with small apolipoprotein(a) phenotypes  and prospective findings in the Bruneck study have revealed a significant association specifically between small apolipoprotein(a) phenotypes and advanced atherosclerotic disease involving a component of plaque thrombosis . Indeed, Lp(a) is a “sticky” lipoprotein that self-aggregates, attaches to all sorts of surfaces , and precipitates not only in vitro but possibly in vivo. Moreover, Lp(a) binds to proteoglycans and glycosaminoglycans  and it has high affinity for fibronectin , tetranectin , collagen , and other connective-tissue structures . Therefore the influence of Lp(a) on platelet aggregation induced with various triggers was investigated measuring serotonin release and thromboxane A2 formation during collagen-triggered aggregation as well as adhesion of platelets to collagen in flowing blood under the influence of Lp(a). As Lp(a) represents an LDL-like particle an elevated platelet reactivity was expected under the influence of this lipoprotein similar to that described for LDL .
Unlike LDL, Lp(a) revealed no proaggregatory effects on platelets, contrary collagen-induced platelet aggregation was inhibited by up to 54% and the aggregation rate was attenuated by 47% compared with platelets incubated with Tyrode’s solution (Fig. 2), being accompanied by a significant reduction of serotonin release and TXA2 formation. Furthermore Lp(a) significantly reduced platelet adhesion to collagen by about 20% and the size of platelet aggregates up to 63% especially at high shear rates (Fig. 3) suggesting that Lp(a) exerts antiaggregatory effects at least under well-defined in vitro conditions . If these observations are relevant for the in vivo situation, a variety of potential platelet-collagen binding sites such as GPIa/IIa or GPIV could be covered by Lp(a) the more that binding of Lp(a) to platelets could be demonstrated . As there is conflicting evidence on the role of Lp(a) in thrombosis in vivo and in vitro work has been done to elucidate the mechanisms whereby Lp(a) is influencing platelet aggregation and a variety of mechanisms is suggested how Lp(a) interferes with platelet aggregation and hence fibrin bound clot formation. Lp(a) binds to resting, non-stimulated platelets on the IIb subunit of the fibrinogen (IIb/IIIa) receptor via binding sites distinct from the arginyl-glycyl-aspartyl (RGD) epitope of apo-a . By this way the RGD binding site of Lp(a) could be exposed via conformational change induced by platelet agonist stimulation leading to binding of the RGD epitope of apo-a to the RGD binding site on the IIb protein of the fibrinogen (IIb/IIIa) receptor of the platelet  thereby reducing fibrinogen binding to the platelet . Low concentrations of Lp(a) (1-25 mg/100 ml washed platelets) increase intracellular levels of c-AMP of in vitro resting platelets leading to an antiaggregatory condition  while at higher in vitro levels of Lp(a) (50-100 mg/100 ml washed platelets) resting platelet intracellular c-AMP levels return to normal  which cannot explain the reported progressive Lp(a)-mediated decrease in collagen-induced aggregation [43, 50]. Further investigations strongly support an apo-a mediated, Lp(a) induced reduction of collagen and ADP-stimulated platelet aggregation via diminished production of thromboxane A2 [43, 51]. Concerning the in vivo situation only one study has been published to date looking at adult human type 2 diabetics all of whom where obese (BMI >30). In this in vivo study of human type 2 diabetics there is a positive correlation between fasting serum concentrations of Lp(a) and bleeding time, a strong correlate of in vivo platelet aggregation  favouring the inhibitory effect of Lp(a) on platelet aggregation. On the other hand there are studies reporting an apparent proaggregatory action of Lp(a) possibly mediated by the apo-a subunit. While no effect of recombinant apo-a [r-apo-a] derivatives on primary ADP-induced platelet aggregation was observed weak platelet responses stimulated by the thrombin receptor-activating peptide SFLLRN were significantly enhanced by the r-apo-a derivatives accompanied by a significant enhancement of [14C]serotonin release of the dense granules . Further investigations showed that r-apo-a isoforms and Lp(a) do not cause platelet aggregation by themselves but preincubation of platelets with r-apo-a derivatives promotes an aggregation response to otherwise subaggregant doses of thrombin receptor activation peptide (TRAP) and arachidonic acid while inversely platelet stimulation with arachidonic acid enhanced platelet binding of apo-a . In both studies it turned out that the size of r-apo-a determined by the number of KIV type 2 modules seems not to play a crucial role in its proaggregant effect.
Summarizing, in vitro studies indicate that Lp(a) induced decreases, increases or no change at all in platelet aggregation [43, 45, 50, 51, 53, 54]. In all cases the mechanisms involved are quite unclear and only speculative. A recent work strongly supports the evidence to suggest that Lp(a) binds to platelets via its arginyl-glycyl-aspartyl (RGD) epitope of the apo(a) but not via apo(a)’s lysine binding region in both strong and weak agonist-stimulated platelets and inhibits the binding of fibrinogen thus reducing aggregation . On the other side there are in vivo studies published quite recently suggesting that Lp(a) concentrations greater than 30 mg/dl are a frequent and independent risk factor for venous thrombosis  and that high levels of Lp(a) could be a more frequently thrombophilic risk factor in young women . To date disagreement exists about increased arterial thrombosis due to elevated blood levels of Lp(a). The fact that this procedure is a result of collagen-exposed platelets in case of plaque rupture followed by clot formation argues against the proaggregatory nature of Lp(a) and maybe procedures others than platelet activation account for the atherogenic nature of Lp(a).
5. Lp(a) and plasminogen
The mechanism by which Lp(a) accelerates atherosclerosis could not yet been clarified. One possible explanation leads via the connection of Lp(a) to the fibrinolytic system as in 1987 it was found out that Lp(a) and plasminogen are immunochemically related  leading to speculations whether Lp(a) might interfere with fibrinolysis. Through partial amino acid sequencing it could be shown for the first time that apo-a has a striking homology of about 70% to plasminogen, the precursor of the proteolytic enzyme plasmin which dissolves fibrin clots . This could be confirmed in our own studies demonstrating that polyclonal antisera from rabbit, sheep and horse as well as three monoclonal antibodies from mouse raised against apo-a reacted with plasminogen on immunoblots and similar to plasminogen, Lp(a) bound selectively but with somewhat lower affinity to lysine-Sepharose . Plasminogen, a protein of 791 amino acids and a molecular weight of about 92 000 D is a plasma serine protease zymogen that consists of five cysteine-rich sequences of 80-114 amino acids each, called kringles, followed by a trypsin like protease domain . The highly glycosylated apo-a exists in various polymorphic forms with molecular weights higher, lower or equal to apoprotein B (Mr ≈ 550 000 D)  which are covalently linked to apoprotein B via disulfide bridges . It contains a hydrophobic signal sequence for secretion followed by up to >50 copies of kringle IV of plasminogen predicting the risk for coronary heart disease in the way that apo-a alleles with a low kringle IV copy number (<22) and high Lp(a) plasma concentration are significantly more frequent in the CHD group (p<0.001) . Additionally one kringle V as well as protease domains of plasminogen are found in apo-a . Later on cDNA sequencing revealed that human apolipoprotein(a) is homologous to plasminogen but despite the fact that apo-a contains a protease domain it does not act fibrinolytically like plasminogen because the arginine at the cleavage site for tissue plasminogen activator in plasminogen is changed to serine in apo-a .
Nevertheless Lp(a) might interfere with the fibrinolytic system in different ways due to its similarity to plasminogen as it may inhibit the binding of plasminogen to its receptor on endothelial cells thereby preventing generation of plasmin and increasing the thrombotic risk [65, 66]. Furthermore it could be demonstrated that Lp(a) accumulates in atherosclerotic lesions maybe via adherence to fibrinogen or fibrin incorporated in atherosclerotic plaques thereby inhibiting fibrinolysis . Another mechanism by which Lp(a) is thought to attenuate fibrinolysis involves direct competition with plasminogen for fibrinogen or fibrin binding sites thus reducing the efficiency of plasminogen activation . Fibrinolysis is initiated by binding of plasminogen to lysine residues on fibrin thereby initiating activation of plasmin and amplifying fibrinolytic processes . Like plasminogen Lp(a) also binds to lysine residues  but without catalytical activity leading to interference with or inhibition of fibrinolysis resulting in hypofibrinolysis and accumulation of cholesterol included in the LDL-like component of Lp(a) . The fact that low molecular weight isoforms of apo-a are associated with greater inhibition of fibrinolysis [70, 71] confirms the hypothesis that subjects with small apo-a phenotypes have a two-fold risk of CHD and stroke compared with those with larger isoforms of apo-a . In contrast Knapp et al.  observed that the rate of plasmin formation was inversely related to Lp(a) but inhibition of plasmin generation increased with the size of apo-a using a standardized in vitro fibrinolysis model. From the fact that the inhibitory effect of free apo-a was much stronger than that of the complete Lp(a) particle they conclude that the apo-a component is responsible for the observed reduction of plasmin formation maybe due to the availability of additional lysine binding sites in the unbound apo-a which was formerly reported by Scanu et al. . On the other hand there are also data showing that the plasma concentration of Lp(a) is inversely related to plasmin formation but that this relationship is not influenced by the size of apo-a isoforms . Above all there are other reports explaining the inhibitory effect of Lp(a) on fibrinolysis not only by competition of Lp(a) with plasminogen for the binding sites on fibrin, endothelial cells and monocytes but also by reduction of tissue plasminogen activator or streptokinase-induced fibrinolytic activity [75, 76, 77].
A novel contribution to the understanding of Lp(a)/apo-a-mediated inhibition of plasminogen activation comes from results showing the ability of the apo(a) component of Lp(a) to inhibit the key positive feedback step of plasmin-mediated conversion of Glu-plasminogen to Lys-plasminogen an essential step for fibrin clot lysis . Interestingly, with the exception of the smallest naturally-occurring isoform of apo(a), isoform size was found not to contribute to the inhibitory capacity of apo(a).
In summary, the proposed mechanisms modulating the antifibrinolytic effects of elevated Lp(a) levels in vitro are manifold and emphasize the prothrombotic effects of this lipoprotein particle. The in vivo situation however seems to be much more complex the more that there is a strong positive correlation reported between bleeding time and fasting serum concentrations of Lp(a) [ 52].
6. Lp(a) and lipid lowering drugs
High levels of Lp(a) are strongly associated with atherosclerosis as revealed by numerous studies [4, 79, 80, 81, 82]. As plasma Lp(a) concentrations above 30 mg/dl, as measured in about 20 percent of white people, are associated with an approx. two-fold relative risk of coronary atherosclerosis  rising to the range of five-fold when LDL and Lp(a) are both elevated  reduction of plasma Lp(a) concentration is recommended. Dietary interventions do not seem to be effective in lowering Lp(a) plasma levels [9, 83] or even lead to an increase of Lp(a) in plasma, alone  or at least when combined with exercise 85]. The same phenomenon could be observed in case of exercise where cross-sectional data suggest that a lifestyle of moderate to intense exercise training does not exert a significant impact on the Lp(a) level [86, 87]. Therefore pharmacological reduction of plasma levels of Lp(a) would be desirable.
Innumerable investigations however indicate that the plasma concentration of Lp(a) is resistant to drug therapy in most cases. As Lp(a) resembles LDL especially with regard to the lipid content (Tab.1) medications reducing LDL-cholesterol should be suitable for lowering Lp(a) as well. Bile acid resins such as cholestyramine which actually cause a significant reduction of LDL-cholesterol as well as of apo-B have no effect on Lp(a) levels [88, 89]. Therapies with bezafibrate or clofibrate [90, 91] showed that there is no role for fibrates in the treatment of elevated Lp(a) concentrations and estrogens also do not seem to significantly affect Lp(a) [92, 93].
Stanozolol, an anabolic steroid used in the treatment of postmenopausal osteoporosis, showed a significant reduction of Lp(a) by about 65% after six weeks therapy but five weeks after the drug was discontinued Lp(a) was near pretreatment levels . Although drastic reductions of Lp(a) up to 40-50% are reported in another study  these compounds seem to be unsuitable for the routine treatment due to their harmful side effects .
Statins, also known as HMG-CoA-reductase inhibitors are another group of lipid lowering drugs which could be interesting with regard to Lp(a). These drugs have proven to be extremely effective in lowering plasma LDL and apo-B levels presumably through inhibition of intracellular cholesterol synthesis concomitant with an increase of the LDL receptors in the liver . Although Lp(a) and LDL are very similar especially concerning the content of cholesterol, inhibitors of HMG-CoA-reductase, the regulating enzyme of cholesterol biosynthesis, show no influence [98, 99], only modest reduction of about 10% [100, 101] or even an increase of serum Lp(a) levels . Altogether the limited magnitude of decrease of Lp(a) by HMG-CoA-reductase inhibitors confirms the assumption that the LDL-receptor does not seem to play a major role in Lp(a) clearance from plasma .
Nicotinic acid, also known as niacin has been shown to lower not only plasma total cholesterol, LDL-cholesterol and triglycerides thereby increasing HDL-cholesterol  but also Lp(a) in a dose-dependent manner up to 40% . A more pronounced effect could be observed in a combination therapy with niacin and neomycin showing a reduction of LDL-cholesterol by 48% and of Lp(a) by 45% respectively . In a recently published study niacin was applied in combination with omega-3-fatty acids and the Mediterranean diet. The average reduction of Lp(a) after 12 weeks combination therapy was reported to be about 23%. Additionally a significant association with increasing baseline levels of Lp(a) was observed .
Diets rich in fish oils containing considerable amounts of omega-3 polyunsaturated fatty acids are recommended to have beneficial effects on plasma lipids thereby lowering the risk of vascular complications [108, 109]. In a study investigating the influence of dietary fish oils on plasma Lp(a) levels a decrease of triglycerides could be observed after six weeks dietary supplementation while total cholesterol, LDL- and HDL-cholesterol as well as Lp(a) remained unchanged . Furthermore collagen- and thrombin-stimulated platelet aggregation and TXB2-formation in platelets decreased by approx. 45% irrespective of the plasma concentration of Lp(a) . This is in agreement with many other studies showing that fish oils only seem to be able to reduce Lp(a) in combination with other therapies  or moderate exercise  but not when used alone [113, 114, 115].
Summarizing it can be shown that increased Lp(a) levels are minimally if at all influenced by drug treatment or drugs reducing Lp(a) to a greater extent like nicotinic acid are not widely used due to undesirable side effects. From previous turnover studies it could be demonstrated that plasma Lp(a) levels correlate with its rate of biosynthesis rather than with the fractional catabolic rate [116, 117] and therefore attempts to reduce Lp(a) should focus on an interference with apo-a biosynthesis. This is supported by the fact that adenovirus-mediated apo-a-antisense RNA expression efficiently inhibits apo-a synthesis in vitro in stably transfected liver cells but also in vivo in transduced mice expressing recombinant human apo-a . In a recently published study it was found that patients suffering from biliary obstructions have very low plasma Lp(a) levels that rise substantially after surgical intervention. Consistent with this, common bile duct ligation in mice transgenic for human apo-a lowered plasma concentrations and hepatic expression of apo-a. Treatment of transgenic mice with cholic acid led to farnesoid X receptor (FXR) activation followed by markedly reduced plasma concentrations and hepatic expression of human apo-a . From that it is concluded that transcription of the apo-a gene is under strong control of the farnesoid X receptor which may have important implications in the development of Lp(a)-lowering medications.
High levels of Lp(a) are strongly associated with atherosclerosis. About 10-15% of the white population exhibit plasma Lp(a) concentrations above the atherogenic cut-off value of approx. 30 mg/dl. Therefore the European Atherosclerosis Society recommended screening for Lp(a) in a consensus report, in which the desirable cut-off was set at less than 50 mg/dl . On the other hand it is very well known that Lp(a) is an inherited atherogenic plasma component determined to more than 90% by genetic factors a fact that aggravates the influence on plasma levels of this lipoprotein. So far there are only speculations about the mechanism by which Lp(a) accelerates atherosclerosis and the exact mechanism could not yet be clarified. Its prothrombotic effects may be ascribed to impaired fibrinolysis by inhibition of plasminogen activation rather than to amplification of platelet aggregation which is shown to be reduced by Lp(a) in most cases. At present dietary interventions or drug therapies seem to be only minimal if at all successful concerning reduction of plasma Lp(a). Up to now it was assumed that the atherogenicity of high Lp(a) levels in blacks must be decreased by other factors . However data published recently show that associations between Lp(a) levels and cardiovascular disease are at least as strong in blacks compared with whites  and emphasize the recommendation that factors such as total cholesterol, LDL-cholesterol, smoking, diabetes mellitus or overweight that can still increase the atherosclerotic risk of Lp(a) should be kept under observation.
Dahlen G. Ericson C. Furberg C. Lundqvist K. Svärdsudd K. 1972Studies on an extra pre-beta lipoprotein fraction. Acta Med. Scand. Suppl. 531 1 29
Albers JJ, Cagana VG, Warnick GR, Hazzard WR 1975Lp(a) lipoprotein-relationship to sinking pre-beta lipoprotein, Hyperlipoproteinemia and apolipoprotein B. Metabolism 24 1047 1052
Armstrong V. W. Cremer P. Eberle E. 1986The association between serum Lp(a) concentrations and angiographically assessed coronary atherosclerosis. Atherosclerosis 62 249 257
Kostner G. M. Avogaro P. Cazzolato G. Marth E. Bittolo-Bon G. Quinci G. B. 1981Lipoprotein Lp(a) and the risk for myocardial infarction. Atherosclerosis 38 51 61
Guyton J. R. Dahlen G. H. Patsch W. Kautz J. A. Gotto A. M. 1985Relationship of plasma lipoprotein Lp(a) levels to race and to apolipoprotein B. Arteriosclerosis 5 265 272
Kostner GM 1976Lp(a) lipoproteins and the genetic polymorphisms of lipoprotein B. From: Low Density Lipoproteins, eds. Day CE, Levy RS. Plenum Press, New York 229 269p.
Bersot TP, Innerarity TL, Pitas RE, Rall jr. SC, Weisgraber KH, Mahley RW 1986Fat feeding in humans induces lipoproteins of density less than 1.006 that are enriched in apolipoprotein(a) and that cause lipid accumulation in macrophages. J. Clin. Invest. 77 622 630
Gries A. Nimpf J. Nimpf M. Wurm H. Kostner G. M. 1987Free and apo-B associated Lp(a)-specific protein in human serum. Clin. Chim. Acta 164 93 100
Krempler F. Kostner G. Bolzano K. Sandhofer F. 1978Studies on the metabolism of the lipoprotein Lp(a) in man. Atherosclerosis 30 57 65
Krempler F. Kostner G. Bolzano K. Sandhofer F. 1979Lipoprotein(a) is not a metabolic product of other lipoproteins containing apolipoprotein B. Biochim. Biophys. Acta 575 63 70
Kronenberg F. Trenkwalder E. Lingenhel A. Friedrich G. Lhotta K. Schober M. Moes N. König P. Utermann G. Dieplinger H. 1997Renovascular arteriovenous differences in Lp[a] plasma concentrations suggest removal of Lp[a] from the renal circulation. J. Lipid Res. 38 1755 1763
Fless GM, ZumMallen ME, Scanu AM 1985Isolation of apolipoprotein(a) from lipoprotein(a). J. Lipid Res. 26 1224 1229
McLean JW, Tomlinson JE, Kuang WJ, Eaton DL, Chen EY, Fless GM, Scanu AM, Lawn RM 1987cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature 330 132 137
Kraft H. G. Kochl S. Menzel H. Sandhofer C. Utermann G. 1992The apolipoprotein(a) gene: a transcribed hypervariable locus controlling plasma lipoprotein(a) concentration. Hum. Genet. 90 220 230
Haibach C. Kraft H. G. Kochl S. Abe A. Utermann G. 1998The number of kringle IV repeats 3-10 is invariable in the human apo(a) gene. Gene 208 253 258
Lackner C. Cohen J. C. Hobbs H. H. 1993Molecular definition of the extreme size polymorphism in apolipoprotein(a). Hum. Mol.Genet. 2 933 940
Brunner C. Lobentanz E. M. Pethö-Schramm A. Ernst A. Kang C. Dieplinger H. Müller H. J. Utermann G. 1996The number of identical kringle IV repeats in apolipoprotein(a) affects its processing and secretion by HepG2 cells. J. Biol. Chem. 271 32403 32410
Maartman-Moe K. Berg K. 1981Lp(a) lipoprotein enters cultured fibroblasts independently of the plasma membrane low density lipoprotein receptor. Clin. Genet. 20 352 362
Armstrong V. W. Walli A. K. Seidel D. 1985Isolation, characterization and uptake in human fibroblasts of an apo(a)-free lipoprotein obtained on reduction of lipoprotein(a). J. Lipid Res. 26 1314 1323
Gries A. Fievet C. Marcovina S. Nimpf J. Wurm H. Mezdour H. Fruchart J. C. Kostner G. M. 1988Interaction of LDL, Lp[a], and reduced Lp[a] with monoclonal antibodies against apoB. J. Lipid Res. 29 1 8
Krempler F. Kostner G. M. Roscher A. Haslauer F. Bolzano K. Sandhofer F. 1983Studies on the role of specific cell surface receptors in the removal of lipoprotein(a) in man. J. Clin. Invest. 71 1431 1441
Berg K. 1963A new serum type system in man- the Lp system. Acta Pathol. Microbiol. Scand. 59 369 382
Harvie NR, Schultz JS 1970Studies of Lpa lipoprotein as a quantitative genetic trait. Proc. Natl. Acad. Sci. USA 66 99 103
Fless GM, Rolih CA, Scanu AM 1984Heterogeneity of human plasma lipoprotein a. J. Biol. Chem. 259 11470 11478
Bersot TB, Innerarity TL, Mahley RW 1984Fat feeding in humans induces lipoproteins of density less than 1.006 that are enriched in apolipoprotein a and that cause lipid accumulation in macrophages. Arteriosclerosis 4: 536a.
Parra MG 1976Isolation of human serum lipoproteins by precipitation and column chromatography methods. Thesis at the University of Marburg/Lahn. Marburg; Mauersperger Press 48 55p.
Rossi EC 1972The function of platelets in hemostasis. Med. Clin. North. Am. 56 25 38
Jaffe R. Dykin D. 1974Evidence for a structural requirement for the aggregation of platelets by collagen. J. Clin. Invest. 53 875 883
Bruckdorfer KR 1989The effect of plasma lipoproteins on platelet responsiveness and on platelet and vascular prostanoid synthesis. Prostaglandins Leukot. Essent. Fatty Acids 38 247 254
Aviram M. Brook J. G. 1987Platelet activation by plasma lipoproteins. Prog. Cardiovasc. Dis. 30 61 72
Aviram M. Brook J. G. 1983Platelet interaction with high- and low-density lipoproteins. Atherosclerosis 46 259 268
Cushing G. L. Gaubatz J. W. Nava M. L. Burdick B. J. Bocan T. M. A. Guyton J. R. Weilbaecher D. ME De Bakey Lawrie. G. M. JD Morrisett 1989Quantitation and localization of apolipoprotein(a) and B in coronary artery bypass vein grafts resected at reoperation. Arteriosclerosis 9 593 603
Ross R. 1993The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362 801 809
Erqou S. Thompson A. Di Saleheen A. E. Kaptoge D. Marcovina S. Danesh S. J. 2010Apolipoprotein(a) isoforms and the risk of vascular disease: a systemic review of 40 studies involving 58,000 participants. J. Am. Coll. Cardiol. 55 2160 2167
Kronenberg F. Kronenberg M. F. Kiechl S. Trenkwalder E. Santer P. Oberhollenzer F. Egger G. Utermann G. Willeit J. 1999Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis: prospective results from the Bruneck study. Circulation 100 1154 1160
Zioncheck TF, Powell LM, Rice GC, Eaton DL, Lawn RM 1991Interaction of recombinant apolipoprotein(a) and lipoprotein(a) with macrophages. J. Clin. Invest. 87 767 771
Bihari-Varga M. Gruber E. Rotheneder M. Zechner R. Kostner G. M. 1988Interaction of lipoprotein(a) and low-density lipoprotein with glycosaminoglycans from human aorta. Arteriosclerosis 8 851 857
Salonen E. Jauhiainen M. Zardi L. Vaheri A. Ehnholm C. 1991Lipoprotein(a) binds to fibronectin and has serine protease activity capable of cleaving it. EMBO J. 8 4035 4040
Kluft C. Jie A. F. H. Los P. De Wit E. Havekes L. 1989Functional analogy between lipoprotein(a) and plasminogen in the binding to the kringle 4 binding protein tetranectin. Biochem. Biophys. Res. Comm. 161 427 433
McConathy WJ, Trieu VN 1991Lp(a) interactions. Prog. Lipid Res. 30 195 203
Kostner G. M. Grillhofer H. 1991Lipoprotein(a) mediates high affinity low density lipoprotein association to receptor negative fibroblasts. J. Biol. Chem. 266 21287 21292
Surya II, Akkerman JWN 1993The influence of lipoproteins on blood platelets. Am. Heart J. 125 272 274
Gries A. Gries M. Wurm H. Kenner T. Ijsseldijk M. Sixma J. J. Kostner G. M. 1996Lipoprotein(a) inhibits collagen-induced aggregation of thrombocytes. Arterioscler. Thromb. Vasc. Biol. 16 648 655
Ezratty A. Simon D. I. Loscalzo J. 1993Lipoprotein(a) binds to human platelets and attenuates plasminogen binding and activation. Biochemistry 32 4628 4633
Malle E. Ibovnik A. Steinmetz G. Kostner G. M. Sattler W. 1994Identification of glycoprotein IIb as the lipoprotein(a)-binding protein on platelets: lipoprotein(a) binding is independent of an arginyl-glycyl-aspartate tripeptide located in apolipoprotein(a). Arterioscler. Thromb. 14 345 352
Shattil S. J. Hoxie J. A. Cunningham M. Brass L. F. 1985Changes in the platelet membrane glycoprotein IIb/IIIa complex during platelet activation. J. Biol. Chem. 260 11107 11114
Hu D. D. CA White-Knodle Panzer. Page S. JD Nicholson N. Smith J. W. 1999A new model of dual interacting ligand binding sites on integrin alphaIIbbeta3. J. Biol. Chem. 274 4633 4639
Farndale RW, Winkler AB, Martin BR, Barnes MJ 1992Inhibition of human platelet adenylate cyclase by collagen fibres. Effect of collagen is additive with that of adrenaline, but interactive with that of thrombin. Biochem. J. 282 25 32
Barre DE 2003Apolipoprotein(a) mediates the lipoprotein(a)-induced biphasic shift in human platelet cyclic AMP. Thromb. Res. 112 321 324
Barre DE 2004Apoprotein(a) antagonises the GPIIB/IIIA receptor on collagen and ADP-stimulated human platelets. Front. Biosci. 9 404 410
Barre DE 1998Lipoprotein(a) reduces platelet aggregation via apo(a)-mediated decreases in thromboxane A2 production. Platelets 9 93 96
Barre D. E. Griscti O. Mizier-Barre K. A. Hafez K. 2005Flaxseed oil and lipoprotein(a) significantly increase bleeding time in type 2 diabetes patients in Cape Breton, Nova Scotia, Canada. J. Oleo. Sci. 54 347 354
Rand M. L. Sangrar W. MA Hancock Taylor. D. M. Marcovina S. M. MA Packham Koschinsky. M. L. 1998Apolipoprotein(a) enhances platelet responses to the thrombin receptor-acitvating peptide SFLLRN. Arterioscler. Thromb. Vasc. Biol. 18 1393 1399
Martínez C. Rivera J. Loyau S. Corral J. Gonzalez-Conejero R. Lozano M. L. Vicente V. Anglés-Cano E. 2001Binding of recombinant apolipoprotein(a) to human platelets and effect on platelet aggregation. Thromb. Haemost. 85 686 693
Barre DE 2007Arginyl-glycyl-aspartyl (RGD) epitope of human apolipoprotein (a) inhibits platelet aggregation by antagonizing the IIb subunit of the fibrinogen (GPIIb/IIIa) receptor. Thromb. Res. 119 601 607
Von Depka. M. Nowka-Göttl U. Eisert R. Dieterich C. Barthels M. Scharrer I. Ganser A. Ehrenforth S. 2000Increased lipoprotein (a) levels as an independent risk factor for venous thromboembolism. Blood 96 3364 3368
Casals F. Escolar G. Deulofeu R. Casals E. 2007Elevated lipoprotein (a) [Lp(a)] levels: a biological marker of venous thromboembolic risk frequently found in young females. Thromb. Res. 119 (Suppl. 1): S 100.
Eaton DL, Fless GL, Kohr WJ, McLean JW, Xu QT, Miller CG, Lawn RM, Scanu AM 1987Partial amino acid sequence of apolipoprotein(a) shows that it is homologous to plasminogen. Proc. Natl. Acad. Sci. USA 84: 3224-3228 (1987)
Karàdi I. Kostner G. M. Gries A. Nimpf J. Romics L. Malle E. 1988Lipoprotein (a) and plasminogen are immunochemically related. Biochim. Biophys. Acta 960 91 97
Brown MS, Goldstein JL 1987Teaching old dogmas new tricks. Nature 330 113 114
Seman LJ, Breckenridge WC 1986Isolation and partial characterization of apolipoprotein (a) from human lipoprotein (a). Biochem Cell Biol. 64 999 1009
Mondola P. Reichl D. 1982Apolipoprotein B of lipoprotein(a) of human plasma. Biochem. J. 208 393 398
Kraft H. G. Lingenhel A. Köchl S. Hoppichler F. Kronenberg F. Abe A. Mühlberger V. Schönitzer D. Utermann G. 1996Apolipoprotein(a) kringle IV repeat number predicts risk for coronary heart disease. Arterioscler. Thromb. Vasc. Biol. 16 713 719
McLean JW, Tomlinson JE, Kuang WJ, Eaton DL, Chen EY, Fless GM, Scanu AM, Lawn RM 1987cDNA sequence of human apolipoprotein(a) is homologous to plasminogen. Nature 12 132 137
Miles LA, Fless GM, Levin EG, Scanu AM, Plow EF 1989A potential basis for the thrombotic risks associated with lipoprotein(a). Nature 339 301 303
Hajjar K. A. Gavish D. Breslow J. L. Nachman R. L. 1989Lipoprotein(a) modulation of endothelial cell surface fibrinolysis and its potential role in atherosclerosis. Nature 339 303 305
Rahman M. N. Petrounevitch V. Jia Z. Koschinsky M. L. 2001Antifibrinolytic effect of single apo(a) kringle domains: relationship to fibrinogen binding. Prot. Eng. 14 427 438
Lijnen H. R. Bachmann F. Collen D. Ellis V. Pannekoek H. Rijken D. C. Thorsen S. 1994Mechanism of plasminogen activation. J. Intern. Med. 236 415 424
Harpel PC, Gordon BR, Parker TS 1989Plasmin catalyzes binding of lipoprotein(a) to immobilized fibrinogen and fibrin. Proc. Natl. Acad. Sci. USA 56 3847 3851
Hervio L. MJ Chapman Thillet. J. Loyau S. Angles-Cano E. 1993Does apolipoprotein(a) heterogeneity influence lipoprotein(a) effects on fibrinolysis? Blood 82 392 397
Undas A. Stepien E. Tracz W. Szczeklik A. 2006Lipoprotein(a) as a modifier of fibrin clot permeability and susceptibility to lysis. J. Thromb. Haemost. 4 973 975
Knapp J. P. Herrmann W. 2004In vitro inhibition of fibrinolysis by apolipoprotein (a) and lipoprotein (a) is size- and concentration-dependent. Clin. Chem. Lab. Med. 42 1013 1019
Scanu A. M. Miles L. A. Fless G. M. Pfaffinger D. Eisenbart J. Jackson E. Hoover-Plow J. L. Brunck T. Plow E. F. 1993Rhesus monkey lipoprotein (a) binds to lysine Sepharose and U937 monocytoid cells less efficiently than human lipoprotein(a). Evidence for the dominant role of kringle 4(37). J. Clin. Invest. 91 283 291
Testa R. Marcovina S. M. 1999The rate of plasmin formation after in vitro clotting is inversely related to lipoprotein(a) plasma levels. Int. J. Lab. Res. 29 128 132
Edelberg J. M. Gonzalez-Gronow M. Pizzo S. V. 1989Lipoprotein(a) inhibits streptokinase-mediated activation of human plasminogen. Biochemistry 28 2370 2374
Edelberg J. M. Gonzalez-Gronow M. Pizzo S. V. 1990Lipoprotein(a) inhibition of plasminogen activation by tissue-type plasminogen activator. Thromb. Res. 57 155 162
Donders SHJ, Lustermans FATh, van Wersch JWJ 1993On lipoprotein(a) and the coagulation/fibrinolysis balance in the acute phase of deep venous thrombosis. Fibrinolysis 7 83 86
Feric NT, Boffa MB, Johnston SM, Koschinsky ML 2008Apolipoprotein(a) inhibits the conversion of Glu-plasminogen to Lys-plasminogen: a novel mechanism for lipoprotein(a)-mediated inhibition of plasminogen activation. J. Thromb. Haemost. 6 2113 2120
Költringer P. Jürgens G. 1985A dominant role of lipoprotein(a) in the investigation and evaluation of parameters indicating the development of cervical atherosclerosis. Atherosclerosis 58 187 198
Murai A. T. Miyahara T. Fujimoto N. Matsuda M. Kameyama M. 1986Lp(a) as a risk factor for coronary heart disease and cerebral infarction. Atherosclerosis 59 199 204
Rhoads G. G. Dahlen G. Berg K. Morton N. E. Dannenberg A. L. 1986Lp(a) lipoprotein as a risk factor for myocardial infarction. J. Am. Med. Ass. 356 2540 2544
Nordestgaard B. G. MJ Chapman Ray. K. Borén J. Andreotti F. Watts G. F. Ginsberg H. Amarenco P. Catapano A. Descamps O. S. Fisher E. Kovanen P. T. Kuivenhoven J. A. Lesnik P. Masana L. Reiner Z. Taskinen M. R. Tokgözoglu L. Tygjaerg-Hansen A. 2010Lipoprotein(a) as a cardiovascular risk factor: current status. Eur. Heart J. 31 2844 2853
Mackinnon L. T. Hubinger L. Lepre F. 1997Effects of physical activity and diet on lipoprotein(a). Med. Sci. Sports Exerc. 29 1429 1436
Randall O. S. Feseha H. B. Illoh K. Xu S. Ketete M. Kwagyan J. Tilghman C. Wrenn M. 2004Response of lipoprotein(a) levels to therapeutic life-style change in obese African-Americans. Atherosclerosis 172 155 160
Ahmadi N. Eshaghian S. Huizenga R. Sosnin K. Ebrahimi R. Siegel R. 2011Effects of intense exercise and moderate caloric restriction on cardiovascular risk factors and inflammation. Am. J. Med. 124 978 982
Hubinger L. Mackinnon L. T. Lepre F. 1995Lipoprotein(a) [Lp(a)] levels in middle-aged male runners and sedentary controls. Med. Sci. Sports Exerc. 27 490 496
Mackinnon LT, Hubinger LM 1999Effects of exercise on lipoprotein(a). Sports Med. 28 11 24
Vessby B. Kostner G. Lithell H. Thomis J. 1982Diverging effects of cholestyramine on apolipoprotein B and lipoprotein Lp(a). Atherosclerosis 44 61 71
AS Dobs Prasad. M. Goldberg A. Guccione M. Hoover D. R. 1995Changes in serum lipoprotein(a) in hyperlipidemic subjects undergoing long-term treatment with lipid-lowering drugs. Cardiovasc. Drugs Ther. 9 677 684
Kostner G. Klein G. Krempler F. 1984Can serum Lp(a) concentration be lowered by drugs and/or diet? In: Carlson LA and Olsson AG (eds.): Treatment of Hyperlipoproteinemia, Raven Press, New York, 151 156p.
Neele D. M. Kaptain A. Huisman H. de Wit E. C. Princen H. M. 1998No effect of fibrates on synthesis of apolipoprotein(a) in primary cultures of cynomolgus monkey and human hepatocytes: apolipoprotein A-I synthesis increased. Biochem. Biophys. Res. Commun. 244 374 378
Christodoulakos GE, Lambrinoudaki IV, Panoulis CP, Papadias CA, Kouskouni EE, Creatsas GC 2004Effect of hormone replacement therapy, tibolone and raloxifene on serum lipids, apolipoprotein A1, apolipoprotein B and lipoprotein(a) in Greek postmenopausal women. Gynecol. Endocrinol. 18 244 257
Persson L. Henriksson P. Westerlund E. Hovatta O. Angelin B. Rudling M. 2012Endogenous estrogens lower plasma PCSK9 and LDL cholesterol but not Lp(a) or bile acid synthesis in women. Arterioscler. Thromb. Vasc. Biol. 32 810 814
Albers J. J. Taggart H. M. Applebaum-Bowden D. Haffner S. Chesnut C. H. Hazzard W. R. 1984Reduction of lecithin-cholesterol acyl-transferase, apolipoprotein D and the Lp(a) lipoprotein with the anabolic steroid stanozolol. Biochim. Biophys. Acta 795 293 296
Hartgens F. Rietjens G. Keizer H. A. Kuipers H. Wolffenbuttel B. H. 2004Effects of androgenic-anabolic steroids on apolipoproteins and lipoprotein(a). Brit. J. Sports Med. 38 253 259
Kostner KM, Kostner GM 2005Therapy of hyper-Lp(a). Handb. Exp. Pharmacol. 170 519 536
Ma Gil P. T. S. Sudhof G. Bilheimer J. C. Goldstein D. W. Brown J. L. MS 1986Mevinolin, an inhibitor of cholesterol synthesis, induces mRNA for low density lipoprotein receptor in liver of hamsters and rabbits. Proc. Nat. Acad. Sci. USA 83 8370 8374
Thiery J. Armstrong V. W. Schleef J. Creutzfeld C. Creutzfeld W. Seidel D. 1988Serum lipoprotein Lp(a) concentrations are not influenced by an HMG-CoA reductase inhibitor. Klin. Wochenschr. 66 462 463
Kostner G. M. Gavish D. Leopold B. Bolzano D. MS Weintraub Breslow. J. L. 1989HMG-CoA reductase inhibitors lower LDL cholesterol without reducing Lp(a) levels. Circulation 80 1313 1319
MS Joy-Lavender Dornbrook. Chin K. A. Hogan H. Denu-Ciocca S. L. C. 2008Effects of atorvastatin on Lp(a) and lipoprotein profiles in hemodialysis patients. Ann. Pharmacother. 42 9 15
Horimoto M. Hasegawa A. Takenaka T. Fujiwara M. Inoue H. Igarashi K. 2003Long-term administration of pravastatin reduces serum lipoprotein(a) levels. Int. J. Clin. Pharmacol. Ther. 41 524 530
Choi S. H. Chae A. Miller E. Messig M. Ntanios F. De Maria A. N. Nissen S. E. Witztum J. L. Tsimikas S. 2008Relationship between biomarkers of oxidized low-density lipoprotein, statin therapy, quantitative coronary angiography, and atheroma: volume observations from the REVERSAL (Reversal of atherosclerosis with aggressive lipid lowering) study. J. Am. Coll. Cardiol. 52 24 32
Hobbs HH, White Al 1999Lipoprotein(a): intrigues and insights. Curr. Opin. Lipidol. 10 225 236
Digby JE, Lee JM, Choudhury RP 2009Nicotinic acid and the prevention of coronary artery disease. Curr. Opin. Lipidol. 20 321 326
Linke A. Sonnabend M. Fasshauer M. Höllriegel R. Schuler G. Niebauer J. Stumvoll M. Blüher M. 2009Effects of extended-release niacin on lipid profile and adipocyte biology in patients with impaired glucose tolerance. Atherosclerosis 205 207 213
Gurakar A. Hoeg J. M. Kostner G. Papadopoulos N. M. Brewer jr H. B. 1985Levels of lipoprotein Lp(a) decline with neomycin and niacin treatment. Atherosclerosis 57 293 301
Helmbold A. F. Slim J. N. Morgan J. Castillo-Rojas L. M. Shry E. A. Slim A. M. 2010The effects of extended release niacin in combination with omega 3 fatty acid supplements in the treatment of elevated lipoprotein (a). Cholesterol 2010: 306147.
Harris WS 1989Fish oils and plasma lipid and lipoprotein metabolism in humans: a critical review. J. Lipid Res. 30 785 807
Wei MY, Jacobson TA 2011Effects of eicosapentaenoic acid versus docosahexaenoic acid on serum lipids: a systematic review and meta-analysis. Curr. Atheroscler. Rep. 13 474 483
Gries A. Malle E. Wurm H. Kostner G. M. 1990Influence of dietary fish oils on plasma Lp(a) levels. Thromb. Res. 58 667 668
Malle E. Sattler W. Prenner E. Leis H. J. Hermetter A. Gries A. Kostner G. M. 1991Effects of dietary fish oil supplementation on platelet aggregability and platelet membrane fluidity in normolipemic subjects with and without high plasma Lp(a) concentrations. Atherosclerosis 88 193 201
Herrmann W. Biermann J. Kostner G. M. 1995Comparison of effects of N-3 to N-6 fatty acids on serum levels of lipoprotein(a) in patients with coronary artery disease. Am. J. Cardiol. 76 459 462
Marckmann P. Bladbjerg E. M. Jespersen J. 1997Dietary fish oil (4 g daily) and cardiovascular risk markers in healthy men. Arterioscler. Thromb. Vasc. Biol. 17 3384 3391
Beavers K. M. Beavers D. P. Bowden R. G. Wilson R. L. Gentile M. 2009Effect of over-the-counter fish-oil administration on plasma Lp(a) levels in an end-stage renal disease population. J. Ren. Nutr. 19 443 449
Kooshki A. Taleban F. A. Tabibi H. Hedayati M. 2011Effects of omega-3 fatty acids on serum lipids, lipoprotein (a), and hematologic factors in hemodialysis patients. Ren. Fail. 33 892 898
Krempler F. Kostner G. M. Bolzano K. Sandhofer F. 1980Turnover of lipoprotein (a) in man. J. Clin. Invest. 65 1483 1490
Rader D. J. Cain W. Ikewaki K. Talley G. Zech L. A. Usher D. Brewer H. B. Jr 1994The inverse association of plasma lipoprotein(a) concentrations with apolipoprotein(a) isoform size is not due to differences in Lp(a) catabolism but to differences in production rate. J. Clin. Invest. 93 2758 2763
Frank S. Gauster M. Strauss J. Hrzenjak A. Kostner G. M. 2001Adenovirus-mediated apo(a)-antisense-RNA expression efficiently inhibits apo(a) synthesis in vitro and in vivo. Gene Therapy 8 425 430
Chennamsetty I. Claudel T. Kostner K. M. Baghdasaryan A. Kratky D. Levak-Frank S. Frank S. Gonzalez F. J. Trauner M. Kostner G. M. 2011Farnesoid X receptor represses hepatic human APOA gene expression. J. Clin. Invest. 121 3724 3734
Virani S. S. Brautbar A. Davis B. C. Nambi V. Hoogeveen R. C. Sharrett A. R. Coresh J. Mosley T. H. JD Morrisett Catellier. D. J. Folsom A. R. Boerwinkle E. Ballantyne C. M. 2012Associations between lipoprotein(a) levels and cardiovascular outcomes in black and white subjects: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 125 241 249