Human urotensin II induces tissue factor and cellular adhesion molecules expression in human coronary endothelial cells: an emerging role for urotensin II in cardiovascular disease.
BACKGROUND
Human urotensin II is an 11-aminoacid peptide with a controversial role in the human cardiovascular system. Indeed, urotensin effects on vascular reactivity and in heart failure are well documented, while its potential role in the pathophysiology of athero-thrombosis is still unknown. This study investigates the effects of urotensin on tissue factor (TF) and VCAM-1/ICAM-1 expression in human coronary endothelial cells (HCAECs).


RESULTS
Urotensin induced TF-mRNA transcription as demonstrated by real time PCR and expression of TF that was functionally active as demonstrated by procoagulant activity assay. In addition, urotensin induced expression of VCAM-1 and ICAM-1 as demonstrated by FACS analysis. VCAM-1 and ICAM-1 were functionally active because they increased leukocyte adhesivity to HCAECs. Urotensin-induced expression of TF and of VCAM-1/ICAM-1 was mediated through the Rho A-activation of the transcription factor, NF-kappaB, as demonstrated by EMSA. Indeed, lovastatin, an HMG-CoA reductase inhibitor, by modulating the Rho activation, and NF-kappaB inhibitors, suppressed the urotensin effects on TF and CAMs.


CONCLUSIONS
Data of the present study, although in vitro, describe the close relationship existing between urotensin II and athero-thrombosis, providing for the first time support for the view that this peptide might have not only vasoactive functions but it might be an effector molecule able to induce a pro-atherothrombotic phenotype in cells of the coronary circulation. Although future studies are required to clarify whether these mechanisms are also important in the clinical setting, this report supports an emerging new role for urotensin II in the pathogenesis and progression of cardiovascular disease.
Cirillo
P
P
Division of Cardiology, University of Naples Federico II, Naples, Italy. pcirillo@unina.it
De Rosa
S
S
Pacileo
M
M
Gargiulo
A
A
Angri
V
V
Fiorentino
I
I
Prevete
N
N
Petrillo
G
G
De Palma
R
R
Leonardi
A
A
De Paulis
A
A
Chiariello
M
M
D002318:Cardiovascular Diseases / Q000209:etiology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics*; D003331:Coronary Vessels / Q000166:cytology*; D042783:Endothelial Cells / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007962:Leukocytes / Q000166:cytology; D012333:RNA, Messenger / Q000096:biosynthesis; D013925:Thromboplastin / Q000235:genetics*; D014579:Urotensins / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000235:genetics
D015815:Cell Adhesion Molecules; D012333:RNA, Messenger; D014579:Urotensins; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1; D013925:Thromboplastin; C029677:urotensin II