6-Mercaptopurine, monocytes, and atherosclerosis.

Atherosclerosis, the underlying cause of heart attack and stroke, appears to be an inflammatory disease driven by retention of modified lipoproteins in the artery wall.1 Markers of inflammation, such as high sensitivity C-reactive protein, are independent predictors of cardiovascular (CV) events.2 If atherosclerosis truly is an inflammatory disease, then shouldn’t we be able to identify antiinflammatory or immunosuppressive medications that are effective in preventing this disease and reducing its clinical expression? The complexity behind this simple supposition was made clear by reports of an association between use of selective cyclooxygenase-2 inhibitors3 or nonselective cyclooxygenase inhibitors4 and increased risk of CV events. On the other hand, statins can be considered antiinflammatory drugs, because they lower high sensitivity C-reactive protein levels and display a variety of antiinflammatory effects in vitro and as such, provide plenty of data to support this hypothesis, including the results of the JUPITER trial,5 where subjects with low levels of low-density lipoprotein and slightly elevated high sensitivity C-reactive protein greatly benefited from statin treatment in terms of CV rate in less than 2 years. The proliferation signal inhibitors, sirolimus and everolimus, have been used in drug-eluting stents to prevent restenosis, but the processes of neointimal and smooth muscle cell proliferation involved in restenosis are not as prominent in the pathogenesis of atherosclerosis.6 A number of conditions that require treatment with antiinflammatory and immunosuppressive medications are associated with increased risk for atherosclerosis and CV events. Despite the impressive progress in defining the cellular and molecular basis of inflammation and the immune response in atherosclerosis, our understanding of the impact of antiinflammatory drugs on the development of atherosclerosis and subsequent CV events remains surprisingly incomplete. It is in this context that studies by Pols et al7 on the impact of 6-mercaptopurine (6-MP), a metabolite of the immunosuppressive drug azathioprine (AZA), on macrophage recruitment and apoptosis in atherosclerosis are of interest.