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


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 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.


CONCLUSIONS
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.
Ihling
C
C
Department of Pathology, University of Freiburg, Freiburg, Germany. cihling@gmx.de
Szombathy
T
T
Bohrmann
B
B
Brockhaus
M
M
Schaefer
H E
HE
Loeffler
B M
BM
D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001018:Aortic Diseases / Q000150:complications / Q000378:metabolism / Q000473:pathology; D001161:Arteriosclerosis / Q000150:complications / Q000378:metabolism* / Q000473:pathology*; D016282:Aspartic Acid Endopeptidases / Q000032:analysis / Q000378:metabolism*; D002339:Carotid Arteries / Q000378:metabolism / Q000473:pathology; D016893:Carotid Stenosis / Q000150:complications / Q000378:metabolism / Q000473:pathology; D002908:Chronic Disease; D003327:Coronary Disease / Q000150:complications / Q000378:metabolism / Q000473:pathology; D003331:Coronary Vessels / Q000378:metabolism / Q000473:pathology; D018450:Disease Progression; D019332:Endothelin-1 / Q000032:analysis / Q000378:metabolism*; D000072396:Endothelin-Converting Enzymes; D004789:Enzyme Activation; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000378:metabolism / Q000473:pathology; D008323:Mammary Arteries / Q000378:metabolism / Q000473:pathology; D008666:Metalloendopeptidases; D017539:Tunica Intima / Q000378:metabolism / Q000473:pathology; D017540:Tunica Media / Q000378:metabolism / Q000473:pathology
D019332:Endothelin-1; D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; C000606923:ECE1 protein, human; D000072396:Endothelin-Converting Enzymes