Coexpression of endothelin-converting enzyme-1 and endothelin-1 in different stages of human atherosclerosis

Article

关键词: HUMAN CORONARY-ARTERY;    BIG ENDOTHELIN-1;    IMMUNOREACTIVITY;    DISEASE;    TISSUE;    METALLOPROTEASE;    MECHANISM;    PEPTIDE;    LESIONS;    ECE-1;   

DOI  :  10.1161/hc3301.094742

来源: SCIE

【 摘 要 】

Background-Endothelin-converting enzyme (ECE)-1 activates endothelin-1 (ET-1) and may thus contribute to the regulation of vascular tone and cell growth during atherosclerosis. Methods and Results-To evaluate ECE-1 immunoreactivity concerning big ET-1/ET-1, 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 I of advanced carotid plaques (n = 15). Furthermore, we determined ECE-1 activity in the control specimens and in the inflammatory intimal regions of carotid plaques. Double immunolabeling showed that ECE-1 was present in endothelial cells, vascular smooth muscle cells, and macrophages. All ET-1(+) cells were simultaneously ECE-1(+). Most importantly, there were significantly more ET-1 cells in the intima and media when atherosclerosis was in an inflammatory stage than when it was in a noninflammatory stage. Moreover, ECE-1 activity was upregulated in the intima of carotid plaques, although immunohistochemically, there were no significant differences between the number of ECE+ cells in the different compartments of the arterial wall. Conclusion-Together with ET-1, ECE-1 is abundantly present in human arteries and at different stages of atherosclerotic plaque evolution. The upregulation of the ECE-1/ET-1 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 ET-1 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.

【 授权许可】

Free