Urokinase-type plasminogen activator deficiency (uPA-KO) prevented carotid artery ligation-induced vascular remodeling in mice

Baby Martin-McNulty, Lening Zhang, Valdeci da Cunha, Jon Vincelette, John C Rutledge, Ronald Vergona, Mark E. Sullivan, Yi Xin Wang

Research output: Contribution to journalArticle

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Abstract

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 α-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.

Original languageEnglish (US)
Pages (from-to)70-75
Number of pages6
JournalTranslational Research
Volume149
Issue number2
DOIs
StatePublished - Feb 2007

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Urokinase-Type Plasminogen Activator
Carotid Arteries
Ligation
Angiotensin II
Cell proliferation
Adventitia
Cell Proliferation
Blood Vessels
Neointima
Macrophages
Common Carotid Artery
Vascular Remodeling
Smooth Muscle Myocytes
Muscle
Actins

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, medical
  • Public Health, Environmental and Occupational Health

Cite this

Urokinase-type plasminogen activator deficiency (uPA-KO) prevented carotid artery ligation-induced vascular remodeling in mice. / Martin-McNulty, Baby; Zhang, Lening; da Cunha, Valdeci; Vincelette, Jon; Rutledge, John C; Vergona, Ronald; Sullivan, Mark E.; Wang, Yi Xin.

In: Translational Research, Vol. 149, No. 2, 02.2007, p. 70-75.

Research output: Contribution to journalArticle

Martin-McNulty, Baby ; Zhang, Lening ; da Cunha, Valdeci ; Vincelette, Jon ; Rutledge, John C ; Vergona, Ronald ; Sullivan, Mark E. ; Wang, Yi Xin. / Urokinase-type plasminogen activator deficiency (uPA-KO) prevented carotid artery ligation-induced vascular remodeling in mice. In: Translational Research. 2007 ; Vol. 149, No. 2. pp. 70-75.
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