HMG-CoA Reductase Inhibitors: Effects on Chronic Subacute Inflammation and Onset of Atherosclerosis Induced by Dietary Cholesterol

Author(s): R. Kleemann, T. Kooistra

Journal Name: Current Drug Targets - Cardiovascular & Hematological Disorders
Continued as Cardiovascular & Hematological Disorders-Drug Targets

Volume 5 , Issue 6 , 2005


Besides classical risk factors such as hypercholesterolemia and hypertension, chronic subacute inflammation has recently been recognized as an important force driving the development of atherosclerosis, the most common underlying cause of myocardial infarction and stroke. There is compelling evidence that a disturbance of cholesterol homeostasis contributes to the development of a chronic inflammatory state and that inhibitors of HMG-CoA reductase (statins) may dampen inappropriate inflammatory responses. We review the evidence and suggest mechanisms by which dietary cholesterol can induce an atherogenic inflammatory response in liver and vessel wall, with particular emphasis on the time course of this inflammatory response during atherogenesis and the interplay between these tissues. We discuss how statins interfere in this process, and whether they may reduce chronic subacute inflammation via a) their cholesterollowering effect, and/or b) their cholesterol-independent (pleiotropic) vasculoprotective activities. Recent studies performed in (humanized) animal models allow us to distinguish the lipid-lowering??dependent from the lipidlowering ??independent functions of statins. Using these data, we discuss the degree to which the lipid-lowering??dependent and lipid-lowering??independent effects of statins contribute to a reduction of inflammation, allowing estimation of the relevance of pleiotropic statin effects for the human situation.

Keywords: Atherosclerosis, biomarkers, C-reactive protein (CRP), cholesterol, inflammation, HMG-CoA reductase inhibitor, liver, pleiotropic effect, statins

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Article Details

Year: 2005
Page: [441 - 453]
Pages: 13
DOI: 10.2174/156800605774962077

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