Blinding the Monocytes to Protect the Heart

Abstract

Despite the impressive success of statins in lowering cholesterol levels, atherosclerotic heart disease remains the leading cause of death in the Western world. Although a central role for cholesterol, particularly low-density lipoprotein cholesterol, in atherogenesis is undisputed, other contributing factors likely include diabetes mellitus, triglycerides, oxidation of proteins or lipids, and immune responses to self- or bacterial antigens. Whatever the precise agents, an expanding body of evidence strongly implicates inflammation as a final common pathway leading to the formation of unstable atherosclerotic plaques, plaque rupture, and acute myocardial infarction.1,2 Consistent with the hypothesis that inflammation plays an important role in plaque instability, a large, prospective, clinical trial found that elevated levels of high-sensitivity C-reactive protein were a strong predictor of future major cardiovascular events, even in patients who met current American Heart Association guidelines for low-density lipoprotein cholesterol levels.3 Clinical trials are now testing the hypothesis that potent anti-inflammatory drugs, such as methotrexate4 or interleukin-1b,5 can reduce the risk of major cardiovascular events in patients who have suffered myocardial infarctions. Ideally, however, one would prefer a drug that more specifically targets vascular inflammation. In this regard, biological insights into the pathogenesis of atherosclerosis have focused attention on circulating blood monocytes.