Everolimus, a promising medical therapy for coronary heart disease?

Coronary heart disease is mainly caused by atherosclerosis, which is a multifactorial and systemic disease. Lipid metabolism disorder and chronic inflammation are two well accepted mechanisms leading to atherosclerosis. The key initiating process in athrogenesis is lipid retention in subendothelium. Inflammatory activity plays an important role in the whole pathogenesis of atherosclerosis. Recent investigations have demonstrated that rapamycin reduces lipid retention by increasing adipose-tissue lipase activity and decreasing lipoprotein lipase activity. Rapamycin also reduce intracellular lipid accumulation in smooth muscle cells and macrophages. Since rapamycin is a definite immunosuppressive agent, and inflammatory process has been involved in atherosclerosis, the compound would have effect on the progression of atherosclerosis through reducing inflammatory activity. Moreover, rapamycin would protect plaque from rupture by selectively clearing macrophages without affecting vascular smooth muscle cells. Even some in vivo studies demonstrate that rapamycin can notably inhibit the development of atherosclerosis. Rapamycin, especially its analog, everolimus, is a non-toxic, well-tolerated drug suitable for long term use. Clinical experiments demonstrate that everolimus can reduce graft vasculopathy in heart transplant patients. Therefore, we propose that everolimus administered systemically is a promising medical therapy to attenuate atherosclerosis and prevent further adverse events. In addition, rapamycin is a selective and effective mammalian target of rapamycin (mTOR) inhibitor. mTOR acts as a hub for cell metabolism, cell growth and cell survival. Based on previous evidences, we hypotheses that mTOR signaling pathway could play a significant role in the pathogenesis of atherosclerosis. (C) 2009 Elsevier Ltd. All rights reserved.