Cigarette smoking is a known risk factor for arteriosclerosis. In atheromatous plaques, the accumulation of vascular smooth muscle cells (VSMCs) have a phenotype differing from that of their normal contractile type. Nicotine is a major pharmacological agent in cigarette smoke. However, any direct effect of nicotine on VSMCs remains uncertain. We investigated the changes in the expression levels of differentiation markers and activity of mitogen-activated protein kinases (MAPKs) after nicotine exposure for 48 h using human aorta primary smooth muscle cells (HVSMC) differentiated with transforming growth factor-β. The results indicated that HVSMC phenotype changed to a synthetic-like phenotype after nicotine exposure. Nicotine is a factor that can change the expression of differentiation marker proteins in VSMCs. Thus, we proposed that nicotine directly affects the migration of VSMCs from the tunica media to atheromatous plaques in the vascular intima by inducing the transformation from a contractile-type to a synthetic-like type, which occurs before the development of atheromatous plaques. Nicotine is contained in nicotine patches and gums for smoking cessation. There may also promote atheromatous plaque formation. We anticipate that determining this mechanism will lead to new means of preventing and treating plaque formation and development in arteriosclerosis.
Part of the book: Atherosclerosis
Protein glycation is the random, nonenzymatic reaction of sugar and protein induced by diabetes and ageing; this process is quite different from glycosylation mediated by the enzymatic reactions catalysed by glycosyltransferases. Schiff bases form advanced glycation end products (AGEs) via intermediates, such as Amadori compounds. Although these AGEs form various molecular species, only a few of their structures have been determined. AGEs bind to different AGE receptors on the cell membrane and transmit signals to the cell. Signal transduction via the receptor of AGEs produces reactive oxygen species in cells, and oxidative stress is responsible for the onset of diabetic complications. This chapter introduces the molecular mechanisms of disease onset due to oxidative stress, including reactive oxygen species, caused by AGEs generated by protein glycation in a hyperglycaemic environment.
Part of the book: Fundamentals of Glycosylation
A number of studies have shown that foetal nutritional status significantly impacts an unborn child’s long-term health. The developmental origins of health and disease (DOHaD) hypothesis proposes that if a child is undernourished in the foetal period, the child will develop diabetes and hypertension in the future if adequate nutrition is given after birth. Moreover, hyperglycaemia (e.g. gestational diabetes mellitus [GDM]) experienced during foetal life can reportedly cause various complications in children. As diabetes is increasing worldwide, so is GDM, and many studies have been conducted using GDM animal models and GDM cell lines. We examined the effects of streptozotocin-induced diabetes, particularly on the heart of offspring, in rat GDM animal models. We also analysed primary cardiomyocyte cultures isolated from these GDM rats and found that insulin signalling was inhibited in GDM cells, as in the GDM animal models, by increased advanced glycation end products. Furthermore, the effect of eicosapentaenoic acid during pregnancy has been reported in GDM animal models and cells, and the findings indicated the importance of nutritional management for GDM during pregnancy.
Part of the book: Gestational Diabetes Mellitus
With the increasing childbearing age, the number of mothers with diabetes and gestational diabetes is escalating. Maternal hyperglycemia creates an intrauterine hyperglycemic environment via the placenta, which causes signaling abnormalities in various fetal organs due to excessive glycation. This is associated with future disease development in the child. We have shown that insulin signaling defects are induced in fetal cardiomyoblasts using a rat gestational diabetes mellitus model and cellular models. Furthermore, we reported that maternal intake of eicosapentaenoic acid (EPA), an n-3 unsaturated fatty acid, during pregnancy can ameliorate this signaling defect. However, EPA has anti-coagulant effects, and the pollution of marine fish oil, the source for EPA supplements, raises concerns about active intake by pregnant women. Recently, palmitoleic acid, an n-7 unsaturated fatty acid, garnered attention as a candidate functional lipid alternative to EPA because it has been reported to have anti-obesity, lipid metabolism improvement, and cardioprotective effects similar to those of EPA. Palmitoleic acid has cis and trans structural isomers, which differ in their food intake route and metabolism in humans. This article introduces recent findings on the biological functions of palmitoleic acid in lifestyle-related diseases and cardiovascular diseases, ranging from basic research to clinical studies.
Part of the book: Fatty Acids