Increased expression of urotensin II and its cognate receptor GPR14 in atherosclerotic lesions of the human aorta.
Urotensin II (U-II), a novel vasoactive peptide, possesses a wide range of cardiovascular effects. U-II binds a seven transmembrane spanning G-protein coupled receptor termed GPR14. In the present study, we have characterized U-II expression in both carotid and aortic atherosclerotic plaques. Using immunohistochemistry we demonstrated U-II immunoreactivity in endothelial, smooth muscle and inflammatory cells of both carotid and aortic plaques, with a clear propensity for intimal staining. Using quantitative real-time RT-PCR we observed both increased U-II and GPR14 mRNA expression in tissue extracts from abdominal aortic aneurysms. We also extended our PCR analysis to include leukocyte expression of U-II and GPR14. We found that lymphocytes were by far the largest producers of U-II mRNA. In contrast monocytes and macrophages were the largest producers of GPR14 mRNA, with relatively little expression in foam cells, lymphocytes, and platelets. Our findings qualitatively and quantitatively demonstrate increased expression of U-II in atherosclerosis with a large degree of inflammatory cell involvement. These findings suggest a possible role for U-II in the pathophysiology of atherosclerosis.
Bousette
Nicolas
N
Montreal General Hospital, Suite L3-109, 1650 Cedar Avenue, Montreal, Que., Canada H3G 1A4.
Patel
Lisa
L
Douglas
Stephen A
SA
Ohlstein
Eliot H
EH
Giaid
Adel
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001011:Aorta / Q000378:metabolism*; D017544:Aortic Aneurysm, Abdominal / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D002340:Carotid Artery Diseases / Q000378:metabolism* / Q000503:physiopathology / Q000601:surgery; D016894:Endarterectomy, Carotid; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014579:Urotensins / Q000235:genetics / Q000378:metabolism*
D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; C121697:UTS2R protein, human; D014579:Urotensins; C029677:urotensin II