Part of the book: Current Trends in Atherogenesis
The cell composition of the human arterial intima has been intensely studied but is still not well understood. The majority of cell population in normal and atherosclerotic intima is represented by cells expressing smooth muscle α-actin, which are thought to be smooth muscle cells. Some antigens, which are absent in medial smooth muscle cells, were detected in intimal smooth muscle cells. In particular, using 3G5 antipericyte antibody, presence of stellate-shaped pericyte-like resident cells in normal and atherosclerotic human aortic intima has been found. In all analyzed aortic tissue specimens, 3G5+ cells were found to account for more than 30% of the total intimal cell population of undiseased intima. In the atherosclerotic lesions, the number of 3G5+ cells becomes notably lower than that in undiseased intima. The use of 2A7 antibody that identifies activated pericytes revealed the presence of 2A7+ cells in atherosclerotic plaques, while no 2A7+ cells were detected in normal intima. The strongest correlation was established between the number of pericyte-like cells and the content of intimal lipids. The correlation coefficients between the number of pericyte-like cells and collagen content and intimal thickness were greater than the correlation coefficients for smooth muscle cells. On the basis of these findings, pericyte-like cells but not smooth muscle cells or other cell types have been declared to be the key cellular element driving the formation of atherosclerotic lesions. The present chapter aims to detail the abovementioned issues. The present chapter also aims to promote a view that α-smooth muscle actin+ pericyte-like cells represent the key players in the development of atherosclerotic lesions.
Part of the book: Muscle Cell and Tissue
Atherosclerosis and disorders associated with cardiovascular system remain the major problem of modern medicine and the leading cause of mortality in developed countries. According to the current knowledge, atherosclerosis development can begin early in life. Clinically silent early‐stage lesions can be detected in a large population of young adults. Despite substantial progress in the recent years, therapy of atherosclerosis mostly remains limited to plasma lipid profile correction. Moreover, no therapy is currently available for the treatment of asymptomatic early stages of the disease. The existing synthetic drugs could not be used for this purpose, because of the unfavourable risk/benefit ratio and high cost of treatment, which has to be long‐lasting. In this regard, medications based on natural agents with anti‐atherosclerotic activity may offer interesting possibilities. Current research should focus on detection and evaluation of such agents. One of the important tools for anti‐atherosclerotic drug evaluation is a cell‐based model, which allows measurement of intracellular lipid accumulation. Anti‐atherosclerotic activity of various substances can therefore be evaluated by the decrease of intracellular lipid storage. In this chapter, we will discuss the development and application of cellular models based on primary culture of human arterial wall cells that are suitable for detection and measurement of anti‐atherosclerotic activity of various substances. Using these models, several natural agents have been successfully evaluated, which led to the development of pharmaceutical products with anti‐atherosclerotic activity based on botanicals.
Part of the book: Cholesterol Lowering Therapies and Drugs
Low-density lipoprotein (LDL) circulating in human bloodstream is the source of lipids that accumulate in arterial intimal cells in atherosclerosis. In-vitro–modified LDL (acetylated, exposed to malondialdehyde, oxidized with transition metal ions, etc.) is atherogenic, that is, it causes accumulation of lipids in cultured cells. We have found that LDL circulating in the atherosclerosis patients’ blood is atherogenic, while LDL from healthy donors is not. Atherogenic LDL was found to be desialylated. Moreover, only the desialylated subfraction of human LDL was atherogenic. Desialylated LDL is generally denser, smaller, and more electronegative than native LDL. Consequently, these LDL types are multiply modified, and according to our observations, desialylation is probably the principal and foremost cause of lipoprotein atherogenicity. It was found that desialylated LDL of coronary atherosclerosis patients was also oxidized. Complex formation further increases LDL atherogenicity, with LDL associates, immune complexes with antibodies recognizing modified LDL and complexes with extracellular matrix components being most atherogenic. We hypothesized that a nonlipid factor might be extracted from the blood serum using a column with immobilized LDL. This treatment not only allowed revealing the nonlipid factor of blood atherogenicity but also opened the prospect for reducing atherogenicity in patients.
Part of the book: Advances in Lipoprotein Research