Endothelial expression of endothelial nitric oxide synthase and endothelin-1 in human coronary artery disease....

Nitric oxide and endothelin-1 (ET-1) are two major endothelium-derived factors with opposing effects on the function and structure of the vessel wall. We investigated the endothelial expression of endothelial nitric oxide synthase (eNOS) and ET-1 in coronary artery disease (CAD) with special reference to the types of underlying lesions. Immunohistochemistry and in situ hybridization were performed in coronary arteries of heart transplant recipients with (n = 16) and without (n = 11) CAD. All coronary arteries from patients with CAD (n = 23) had concentric fibrous or advanced lesions, whereas most of the arteries (25 of 31) from patients with non-CAD showed normal appearance (myointimal thickening only) or eccentric lesions alone. Normal coronary segments consistently showed apparent endothelial immunoreactivity and mRNA signals for both eNOS and ET-1. In atherosclerotic coronary segments, endothelial expression of eNOS and ET-1 was reduced in most lesion sites, particularly in severe subendothelial lesions with dense fibrosis or macrophage accumulation, but not with smooth muscle cells only. Conversely apparent ET-1, compared with weak or focal eNOS signals, were more frequently seen in coronary segments with concentric severe lesions from CAD but not non-CAD patients. Immunoreactivity and mRNA signals for ET-1 were co-localized with those for ET converting enzyme-1 in the endothelium, as well as in the underlying macrophages and smooth muscle cells. These results indicate the presence of differential endothelial expression of eNOS and ET-1 in diseased human coronary arteries with severe concentric atherosclerotic lesions, a finding that was rare in atherosclerotic lesions of coronary arteries of non-CAD patients. Altered expression of endothelium-derived factors may contribute to abnormality of coronary vasomotor tone and the formation of subendothelial lesions in CAD.