title: Effects of angiotensin II intervention on MMP-2, MMP-9, TIMP-1, and collagen expression in rats with pulmonary hypertension.
abstract: This study investigated the effects of angiotensin II (AngII) intervention, using captopril and losartan, on the expression of matrix metalloproteinase-2 (MMP-2), MMP-9, tissue inhibitor of metalloproteinase-1 (TIMP-1), and collagen in rats with pulmonary hypertension, in an effort to understand mechanisms underlying pulmonary vascular remodeling. A total of 40 male Sprague-Dawley rats were randomly divided into normal group, model group, captopril group, and losartan group. After 5 weeks, the mean pulmonary arterial pressure (mPAP), right ventricular index, and neointima formation in each group were determined. Immunohistochemical analysis was performed to determine the degree of pulmonary arterial muscularization as well as MMP-2, MMP-9, and TIMP-1 protein expression in lung tissue. Real-time fluorescent quantitative PCR was used to detect MMP2, MMP9, TIMP1, COL1A1, and COL4A1 mRNA expression. Picro-sirius red staining was performed to detect collagen protein expression. Neointima formation was observed in the model group. Moreover, the mPAP, right ventricular index, degree of arterial muscularization, and collagen deposition, as well as mRNA and protein expression of MMP2, MMP9, and TIMP1 were significantly higher than those in the other groups (P < 0.05). The mPAP, right ventricular index, degree of arterial muscularization, and mRNA and protein expression in the captopril and losartan groups were significantly decreased compared with those of the model group (P < 0.05). AngII regulates MMP-2, MMP-9, and TIMP-1 expression and affects collagen deposition. Thus, this hormone is involved in pulmonary vascular remodeling, indicating a possible mechanism that can be targeted in pulmonary hypertension intervention.
authors: Department of Pediatric Cardiology, Chengdu Women's and Children's Central Hospital, Chengdu, China wxm6910@126.com.
authors: X M
authors: XM
authors: Wang
authors: Department of Pediatric Cardiology, Chengdu Women's and Children's Central Hospital, Chengdu, China.
authors: K
authors: K
authors: Shi
authors: Department of Pediatric Rehabilitation, Zhengzhou Children's Hospital, Zhengzhou, China.
authors: J J
authors: JJ
authors: Li
authors: Department of Pediatric Cardiology, Chengdu Women's and Children's Central Hospital, Chengdu, China.
authors: T T
authors: TT
authors: Chen
authors: Department of Pediatric Cardiology, Chengdu Women's and Children's Central Hospital, Chengdu, China.
authors: Y H
authors: YH
authors: Guo
authors: Department of Pediatric Cardiology, Chengdu Women's and Children's Central Hospital, Chengdu, China.
authors: Y L
authors: YL
authors: Liu
authors: Department of Pediatric Cardiology, Chengdu Women's and Children's Central Hospital, Chengdu, China.
authors: Y F
authors: YF
authors: Yang
authors: Department of Pediatric Cardiology, Chengdu Women's and Children's Central Hospital, Chengdu, China.
authors: S
authors: S
authors: Yang
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism*; D000090602:Collagen Type I, alpha 1 Chain; D024141:Collagen Type IV / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000235:genetics*; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024141:Collagen Type IV; D012333:RNA, Messenger; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D000804:Angiotensin II; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat