Cholesterol lowering and endothelial function.
The pathophysiology of the association between cholesterol and atherosclerosis has been thought to involve the deposition, modification, and cellular uptake of cholesterol. We now believe that the process begins with vascular injury and involves inflammation and vessel remodeling. The vascular endothelium actively regulates vascular tone, lipid breakdown, thrombogenesis, inflammation, and vessel growth, all of which are important factors in the development of atherosclerosis. Endothelial dysfunction promotes atherosclerosis through vasoconstriction, monocyte and platelet adhesion, thrombogenesis, and cytokine and growth factor stimulation and release. An important component of endothelial dysfunction is reduced availability of nitric oxide, which is caused by low-density lipoproteins, especially if they are oxidized. This reduced availability appears to occur through a combination of decreased production, abnormal signaling, and increased destruction by oxygen-free radicals. Concurrently, endothelium-mediated vasoconstrictors, adhesion molecules, cytokines, growth factors, and thrombogenic factors, such as endothelin, are increased by oxidized low-density lipoprotein. Several studies have shown improvements in endothelial function with cholesterol lowering, which may explain the early and substantial reductions in major cardiovascular events associated with cholesterol lowering.
Vogel
R A
RA
Department of Medicine, University of Maryland School of Medicine, Baltimore, USA.
D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D001781:Blood Component Removal; D002784:Cholesterol / Q000097:blood*; D002986:Clinical Trials as Topic; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*
D000924:Anticholesteremic Agents; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D002784:Cholesterol