Cholesterol, cholesterol lowering, and endothelial function

R. A. Vogel, M. C. Corretti, J. Gellman

Research output: Contribution to journalArticlepeer-review

Abstract

A strong relationship between hypercholesterolemia and atherosclerosis has been established through epidemiological, experimental, and clinical trial data. Traditional theories on the pathophysiology of this relationship involve the deposition, modification, and cellular uptake of cholesterol, and the release of inflamatory and growth factors resulting in smooth muscle cell proliferation and collagen matrix production. The vasculature has recently been found to be an active and complex organ, with the endothelium playing a controlling role in vascular tone, lipid breakdown, thrombogenesis, inflammation, and vessel growth. In the presence of risk factors such as hypercholesterolemia, the endothelium promotes vasoconstriction, monocyte and platelet adhesion, thrombogenesis, and growth factor release. A high-fat diet also directly impairs endothelial function and increases coagulation factors. Endothelial dysfunction is associated with decreased availability of the predominant vasodilator nitric oxide, possibly by increased destruction by oxygen free radicals. This dysfunctional state appears before the earliest anatomic evidence of atherosclerosis and may represent an important initial step in its development. Several studies have shown improvements in endothelial function with cholesterol lowering in both normal individuals and those with coronary head disease. Short-term improvements in endothelial- dependent vasodilation and adhesion molecule expression have also been reported with antioxidant therapy. These observations suggest that atherosclerosis is at least in part caused by endothelial dysfunction that favors cellular proliferation. This new understanding helps to explain the early and substantial reductions in major cardiovascular events associated with cholesterol lowering.

Original languageEnglish (US)
Pages (from-to)117-136
Number of pages20
JournalProgress in Cardiovascular Diseases
Volume41
Issue number2
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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