[Pathogenesis of atherosclerosis in patients with lipid metabolism disturbances: hypothesis on cholesterol utilization and atheromatous plaque formation].
Cholesterol is known to participate in atheromatous plaque formation coming from blood stream and affecting vascular endothelium in environment of elevated low-density lipoproteins (LDL). Nevertheless, the occurrence of single atheromatous plaque evidences the possibility of local lipoprotein accumulation by vascular wall without systemic increase in serum LDLs. The author hypothesizes that in the absence of hypercholesterolemia atheroma can evolve through the utilization of modified LDL and free or etherified cholesterol, that remain in media non-removed by high density lipoproteins (HDL) owing to their structural damage after local vascular wall ischemia caused by vasa vasorum disorders. Disturbances in HDL acceptor function and transport of cholesterol and modified LDL to blood circulation and further into liver are followed by local accumulation of these products in smooth muscle cells. Overloaded by lipids smooth muscle cells move through internal fenestrated membrane thus activating receptor mechanism for transmission of modified lipoproteins to monocytes and capture of endothelial membrane and amorphous lipids by them in local lipid peroxidation area. A framework for hypothesis experimental and clinical testing is suggested.
Chepelenko
G V
GV
Department of angiography and reentgenography, N. A. Semashko Central Clinical Hospital, Ministry of Railway Transport, Moscow, Russia.
D008076:Cholesterol, HDL / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism; D003324:Coronary Artery Disease / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications* / Q000378:metabolism*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D015227:Lipid Peroxidation / Q000502:physiology; D009130:Muscle, Smooth / Q000378:metabolism; D010982:Platelet-Derived Growth Factor / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D016212:Transforming Growth Factor beta / Q000378:metabolism; D053773:Transforming Growth Factor beta1; D014651:Vasa Vasorum / Q000378:metabolism / Q000503:physiopathology
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; C524898:PLAUR protein, human; D010982:Platelet-Derived Growth Factor; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C075278:platelet-derived growth factor A; D007334:Insulin-Like Growth Factor I