Neuroimmunologic implications in coronary artery disease

In this review, the role of the macrophage in the pathophysiology of coronary artery disease (CAD) is examined. The central interaction of macrophage, endothelial cell and smooth muscle cell in the context of hyperlipidemia is considered. The macrophage appears to be at the beginning of a chain of events that starts with elevated low density lipoprotein (LDL). Stress, particularly in those with a core hostility, may be associated not only with higher catecholamine levels but also with higher serum lipid levels. These lipids will in turn be processed to oxidized LDL by macrophage and endothelial cells. Oxidized LDL molecules will contribute to atherosclerotic plaquing. A side effect of such plaque formation may be a diminished vasodilatory response to the nitric oxide (NO) produced by macrophages and endothelium. Indeed, paradoxical vasoconstriction occurs in atherosclerosis in response to neurotransmitters such as serotonin and acetylcholine, which under normal circumstances cause vasodilation. There also is evidence that both macrophages and endothelial cells can regulate NO production through a specific μ3 morphine receptor, an effect that can be blocked by naloxone. The clinical effectiveness of morphine and nitroglycerin in CAD patients may relate to these mechanisms. More research will be needed to elucidate the neuroimmunologic basis for atherosclerosis with prospects for better treatment and management in future.