title: Atherosclerosis regulation via media lipid-driven VSMC cholesterol efflux switch.
abstract: It is known, that initial events in atherosclerosis arise in the intima with a parallel influx of inflammatory cells. I propose the opposite - that the disease onset begins from the media vascular smooth muscle cell (VSMC) involvement and through its utilization of modified low-density lipoproteins (LDL), and free or esterified cholesterol. Other oxidized lipoprotein molecules remain in the media which are non-removed by high-density lipoproteins (HDL), owing to their structural damages after local vasa vasorum and adventitia lymphatic disorders. Mechanism by which VSMC ingulf and degrade them includes lipid-driven activation of VSMC reverse cholesterol transport pathways from the media to macrophages, and from the last - to plasma HDL (non-damaged) and apoA-1 or - directly to them. When some of the pathways are impaired, its demands a reprogramming of the existing cholesterol removal route to another, or selective gene involvements and transcriptional regulation of inflammatory signaling. Intima cell call-effects may be linked after their down-regulation with the expression of cytokines, chemokines by migrating VSMC to stem cells for dose-dependent proliferation, VSMC and macrophage maturation in non- and inflammatory phases of early or late atherosclerosis.
authors.affiliation: N.A. Semashko Central Clinical Hospital, Moscow, Russia. Electronic address: chepgenn1@rambler.ru.
authors.forename: G V
authors.initials: GV
authors.lastname: Chepelenko
mesh_terms: D050197:Atherosclerosis / Q000209:etiology* / Q000378:metabolism; D001692:Biological Transport / Q000502:physiology; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008954:Models, Biological; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D017539:Tunica Intima / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D002784:Cholesterol