Blinding the Monocytes to Protect the Heart
Despite the impressive success of HMG-CoA reductase inhibitors (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 LDL-cholesterol in atherogenesis is undisputed, other contributing factors likely include diabetes mellitus, triglycerides, oxidation of proteins and/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 formation of unstable atherosclerotic plaques, plaque rupture, and acute myocardial infarction1,2. Consistent with the hypothesis that inflammation plays an important role in plaque instability, a large prospective clinical trial found that elevated levels of hsCRP were a strong predictor of future major cardiovascular events, even in patients who met current American Heart Association guidelines for LDL-cholesterol levels3. Clinical trials are now testing the hypothesis that potent anti-inflammatory drugs, such as methotrexate4 or IL-1b5, 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.
- Received April 22, 2013.
- Accepted April 22, 2013.