Angiotensin-converting enzyme 2 (ACE2) expression and activity in human carotid atherosclerotic lesions.
Angiotensin-converting enzyme (ACE)2 is a recently identified homologue of ACE. As ACE2 inactivates the pro-atherogenic angiotensin II, we hypothesize that ACE2 may play a protective role in atherogenesis. The spatiotemporal localization of ACE2 mRNA and protein in human vasculature and a possible association with atherogenesis were investigated using molecular histology (in situ hybridization, immunohistochemistry). Also, the ACE : ACE2 balance was investigated using enzymatic assays. ACE2 mRNA was expressed in early and advanced human carotid atherosclerotic lesions. In addition, ACE2 protein was present in human veins, non-diseased mammary arteries and atherosclerotic carotid arteries and expressed in endothelial cells, smooth muscle cells and macrophages. Quantitative analysis of immunoreactivity showed that total vessel wall expression of ACE and ACE2 was similar during all stages of atherosclerosis. The observed ACE2 protein was enzymatically active and activity was lower in the stable advanced atherosclerotic lesions, compared to early and ruptured atherosclerotic lesions. These results suggest a differential regulation of ACE2 activity during the progression of atherosclerosis and suggest that this novel molecule of the renin-angiotensin system may play a role in the pathogenesis of atherosclerosis.
Sluimer
J C
JC
Department of Pathology, University of Maastricht, Cardiovascular Research Institute Maastricht, Maastricht, The Netherlands.
Gasc
J M
JM
Hamming
I
I
van Goor
H
H
Michaud
A
A
van den Akker
L H
LH
Jütten
B
B
Cleutjens
J
J
Bijnens
A P J J
AP
Corvol
P
P
Daemen
M J A P
MJ
Heeneman
S
S
D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D002339:Carotid Arteries / Q000201:enzymology*; D002340:Carotid Artery Diseases / Q000201:enzymology*; D002851:Chromatography, High Pressure Liquid; D042783:Endothelial Cells / Q000201:enzymology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization / Q000379:methods; D008264:Macrophages / Q000201:enzymology; D008297:Male; D008323:Mammary Arteries / Q000201:enzymology; D032389:Myocytes, Smooth Muscle / Q000201:enzymology; D007703:Peptidyl-Dipeptidase A / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D012084:Renin-Angiotensin System / Q000502:physiology; D018709:Statistics, Nonparametric
D012333:RNA, Messenger; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2