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 language | English (US) |
|---|---|
| Pages (from-to) | 70-75 |
| Number of pages | 6 |
| Journal | Translational Research |
| Volume | 149 |
| Issue number | 2 |
| DOIs | |
| State | Published - Feb 2007 |
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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 journal › Article
}
TY - JOUR
T1 - Urokinase-type plasminogen activator deficiency (uPA-KO) prevented carotid artery ligation-induced vascular remodeling in mice
AU - Martin-McNulty, Baby
AU - Zhang, Lening
AU - da Cunha, Valdeci
AU - Vincelette, Jon
AU - Rutledge, John C
AU - Vergona, Ronald
AU - Sullivan, Mark E.
AU - Wang, Yi Xin
PY - 2007/2
Y1 - 2007/2
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33846232141&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33846232141&partnerID=8YFLogxK
U2 - 10.1016/j.trsl.2006.09.002
DO - 10.1016/j.trsl.2006.09.002
M3 - Article
C2 - 17240317
AN - SCOPUS:33846232141
VL - 149
SP - 70
EP - 75
JO - Translational Research
JF - Translational Research
SN - 1931-5244
IS - 2
ER -