Urokinase-type plasminogen activator deficiency (uPA-KO) prevented carotid artery ligation-induced vascular remodeling in mice.
It has been demonstrated that urokinase-type plasminogen activator (uPA) plays an important role in vascular remodeling. This study was designed to determine whether uPA deficiency (KO) affects carotid artery ligation-induced vessel remodeling and the interaction with angiotensin II (Ang II). Ligation of the left common carotid artery in 6-month-old wild-type (C57 black/6J) mice for 4 weeks induced a concentric remodeling with vessel wall thickening, characterized by cell proliferation in neointima, media, and adventitia, and with lumen narrowing without a significant enlargement of overall vessel dimension. Intima lesions were characterized by alpha-actin positive smooth muscle cell (SMC) proliferation in a matrix background. No detectable presence of MAC-3 positive macrophages existed in the vascular wall. The ligation-induced vascular neointimal formation and adventitial proliferation, but not lumen narrowing and media expansion, were completely prevented in age-matched uPA-KO mice. Chronic infusion of Ang II (1.44 mg/kg per day) via a subcutaneously implanted osmotic minipump did not significantly affect the gross morphology of the nonligated carotid artery from both wild-type and uPA-KO mice, but it enhanced ligation-induced vascular remodeling. However, in the presence of Ang II, uPA deficiency had no effects on ligation-induced mophermetric change, but it partially and significantly reduced cell proliferation. These data indicate that uPA may play a critical role in ligation-induced vessel remodeling. Ang II may activate other mechanisms independent of uPA to exacerbate ligation-induced vascular remodeling.
Martin-McNulty
Baby
B
Department of Pharmacology, Berlex Bioscience, Richmond, CA 94806, USA.
Zhang
Lening
L
da Cunha
Valdeci
V
Vincelette
Jon
J
Rutledge
John C
JC
Vergona
Ronald
R
Sullivan
Mark E
ME
Wang
Yi-Xin
YX
D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002340:Carotid Artery Diseases / Q000473:pathology* / Q000503:physiopathology*; D015918:Infusion Pumps, Implantable; D008026:Ligation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014568:Urokinase-Type Plasminogen Activator / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000378:metabolism / Q000494:pharmacology
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D014568:Urokinase-Type Plasminogen Activator