Myocardial 15-epi-lipoxin A4 generation provides a new mechanism for the immunomodulatory effects of statins and thiazolidinediones.

This famous maxim of Louis Pasteur, spoken in 1854 during his inaugural lecture as Professor and Dean at the University of Lille, can be applied today to the fortuitous observation that hydroxymethylglutaryl–coenzyme A (HMG-CoA) reductase inhibitors, in addition to their designed lipid-lowering effects, display a fascinating array of antiinflammatory properties. Post hoc analyses of the West of Scotland Coronary Prevention Study (WOSCOPS) population, and more recently the Cholesterol and Recurrent Events (CARE), Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering (MIRACL), Long-term Intervention With Pravastatin in Ischemic Disease (LIPID), and Heart Protection Study (HPS) trials, have all found benefits conferred by statins that are independent of low-density lipoprotein cholesterol–lowering alone.1 Only through careful analyses of early clinical trials of statins administered for lowering cholesterol and cardiovascular events did scientists uncover additional benefit for these agents in cardiac protection beyond their ability to reduce cholesterol synthesis. Inflammation and immune responses are now appreciated to play pivotal roles in the pathobiology of atherosclerosis,2 and recent clinical and basic investigations have uncovered important immunomodulatory roles for statins.3 Of interest, the peroxisome proliferator-activated receptor family of transcription factors is activated by and cooperates with statins in their antiinflammatory actions. In this issue of Circulation, Birnbaum and colleagues4 present evidence for increased myocardial production of 15-epi-lipoxin (LX)A4 by atorvastatin and the peroxisome proliferator-activated receptorligand pioglitazone. The generation of 15-epi-LXA4 would provide a novel mechanism for immune regulation by statins because this arachidonic acid–derived chalone displays potent antiinflammatory and proresolving properties,5 including many that have also been observed with statins (Table). Article p 929