Regression of atherosclerosis: which components regress and what influences their reversal.
Two major features of atherosclerosis may be distinguished: (a) atherosis caused by lipid infiltration in cells and extracellularly and (b) sclerosis caused by connective tissue deposition and by functional disturbance of the endothelium, leading to impairment of endothelium-derived relaxing factor (EDRF)-release and reduced arterial compliance. Atherosis generally rarely causes clinical symptoms and, furthermore, is reversible by lowering of LDL-C. However, the clinically significant human lesion is the fibrous atheromatous plaque. Regression of established fibrous lesions by maximal lowering of LDL-C is slow in native coronary arteries and nonexistent in bypass grafts. However, there is good evidence from recent clinical trials that even in arteries with significant fibrous plaques, functional improvement of sclerosis (increased compliance) can be achieved by reducing maximally LDL-C in spite of remaining structural connective tissue abnormalities, presumably through normalization of EDRF. Atherosclerosis, therefore, appears to be best influenced by lipid lowering when it is in its atherosis phase. In the plaques of advanced atherosclerosis, when connective tissue sclerosis is present, agents working through mechanisms other than lipid lowering appear to be required for plaque reversal.
Kramsch
D M
DM
Atherosclerosis Research Institute, University of Southern California School of Medicine, Los Angeles.
Blankenhorn
D H
DH
D000818:Animals; D001161:Arteriosclerosis / Q000473:pathology* / Q000628:therapy; D003324:Coronary Artery Disease / Q000473:pathology / Q000628:therapy; D004730:Endothelium, Vascular / Q000473:pathology*; D005500:Follow-Up Studies; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000473:pathology*