
<ArticleTitle>Coexpression of <prot>endothelin-converting enzyme-1</prot> and <prot>endothelin-1</prot> in different stages of human atherosclerosis.</ArticleTitle>
<AbstractText>BACKGROUND: <prot>Endothelin-converting enzyme</prot> (<prot>ECE</prot>)-1 activates <prot>endothelin-1</prot> (<prot>ET-1</prot>) and may thus contribute to the regulation of vascular tone and cell growth during atherosclerosis. METHODS AND RESULTS: To evaluate <prot>ECE-1</prot> immunoreactivity concerning big <prot>ET-1</prot>/<prot>ET-1</prot>, we performed qualitative and quantitative immunohistochemistry in normal internal mammary arteries (n=10), in coronary arteries with adaptive intimal fibrosis (n=10), in aortic fatty streaks (n=10), and in distinct regions of advanced carotid plaques (n=15). Furthermore, we determined <prot>ECE-1</prot> activity in the control specimens and in the inflammatory intimal regions of carotid plaques. Double immunolabeling showed that <prot>ECE-1</prot> was present in endothelial cells, vascular smooth muscle cells, and macrophages. All <prot>ET-1</prot>(+) cells were simultaneously <prot>ECE-1</prot>(+). Most importantly, there were significantly more <prot>ET-1</prot>(+) cells in the intima and media when atherosclerosis was in an inflammatory stage than when it was in a noninflammatory stage. Moreover, <prot>ECE-1</prot> activity was upregulated in the intima of carotid plaques, although immunohistochemically, there were no significant differences between the number of <prot>ECE</prot>(+) cells in the different compartments of the arterial wall. CONCLUSION: Together with <prot>ET-1</prot>, <prot>ECE-1</prot> is abundantly present in human arteries and at different stages of atherosclerotic plaque evolution. The upregulation of the <prot>ECE-1</prot>/<prot>ET-1</prot> system is closely linked to the presence of chronic inflammation and is present in very early stages of plaque evolution. Therefore, enhanced production of active <prot>ET-1</prot> may substantially contribute to cell growth and the regulation of vascular tone in advanced atherosclerotic lesions and in the very early stages of plaque evolution, when a plaque is still imperceptible clinically.</AbstractText>
