Cholesterol lowering and endothelial function

The pathophysiology of the association between cholesterol and atherosclero sis 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 endot helium actively regulates vascular tone, lipid breakdown, thrombogenesis, i nflammation, and vessel growth, all of which are important factors in the d evelopment of atherosclerosis. Endothelial dysfunction promotes atheroscler osis through vasoconstriction, monocyte and platelet adhesion, thrombogenes is, and cytokine and growth factor stimulation and release. An important co mponent of endothelial dysfunction is reduced availability of nitric oxide, which is caused by low-density lipoproteins, especially if they are oxidiz ed. This reduced availability appears to occur through a combination of dec reased production, abnormal signaling, and increased destruction by oxygen- free radicals. Concurrently, endothelium-mediated vasoconstrictors, adhesio n molecules, cytokines, growth factors, and thrombogenic factors, such as e ndothelin, are increased by oxidized low-density lipoprotein. Several studi es have shown improvements in endothelial function with cholesterol lowerin g, which may explain the early and substantial reductions in major cardiova scular events associated with cholesterol lowering. Am J Med. 1999;107:479- 487. (C) 1999 by Excerpta Medica, Inc.