Alpha2-antiplasmin is a critical regulator of angiotensin II-mediated vascular remodeling.
OBJECTIVE
Alpha2-antiplasmin (alpha2-AP) is the major circulating inhibitor of plasmin, which plays a determining role in the regulation of intravascular fibrinolysis. We investigated the role of alpha(2)-AP on vascular remodeling in response to angiotensin II (Ang II).


RESULTS
alpha2-AP-deficient mice were performed. Ang II and N(omega)-nitro- L-arginine methyl ester (L-NAME)-induced perivascular fibrosis was significantly decreased in alpha2-AP-/- mice compared with wild-type mice. In situ gelatinolytic activity analysis shows that perivascular gelatinolytic activity was increased in alpha2-AP-/- mice, which was responsible for decreased perivascular fibrosis in response to Ang II and L-NAME. Ang II-induced arterial wall thickening, vascular cell proliferation, apoptosis, c-Myc, and collagen I expression were significantly decreased in alpha2-AP-/- mice compared with wild-type mice. Further analysis shows that increased p53 and p21 expression were responsible for inhibition of Ang II-induced vascular remodeling in alpha2-AP-/- mice.


CONCLUSIONS
The results show that alpha2-AP is a critical regulator for vascular remodeling by inhibiting p53/p21 pathway, suggesting that alpha2-AP is proposed to be a potential therapeutic target for vascular remodeling.
Hou
Yongzhong
Y
Osamu Matsuo and Yongzhong Hou, Department of Physiology, Kinki University School of Medicine, Osaka, Japan. hou_yz@yahoo.com
Okada
Kiyotaka
K
Okamoto
Chikako
C
Ueshima
Shigeru
S
Matsuo
Osamu
O
D000804:Angiotensin II; D000818:Animals; D017209:Apoptosis; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation; D024042:Collagen Type I / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004195:Disease Models, Animal; D005136:Eye Proteins / Q000235:genetics / Q000378:metabolism*; D005355:Fibrosis; D018093:Gelatinases / Q000378:metabolism; D006973:Hypertension / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester; D009414:Nerve Growth Factors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D015843:Serpins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D013895:Thoracic Arteries / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D000099174:Pigment Epithelium-Derived Factor
D000804:Angiotensin II; D024042:Collagen Type I; D050759:Cyclin-Dependent Kinase Inhibitor p21; D005136:Eye Proteins; D018093:Gelatinases; D019331:NG-Nitroarginine Methyl Ester; D009414:Nerve Growth Factors; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D016271:Proto-Oncogene Proteins c-myc; D015843:Serpins; D016159:Tumor Suppressor Protein p53; D000099174:Pigment Epithelium-Derived Factor; C489428:Myc protein, mouse; C052617:Bcl2 protein, mouse