Loss of cavin1 and expression of p-caveolin-1 in pulmonary hypertension: Possible role in neointima formation  

作　　者：Jing Huang Rajamma Mathew 

机构地区：[1]Department of Pediatrics, New York Medical College [2]Department of Physiology, New York Medical College

出　　处：《World Journal of Hypertension》2019年第2期17-29,共13页世界高血压杂志

基　　金：Supported in part by Cardiovascular Medical Research and Education Fund

摘　　要：BACKGROUND Pulmonary hypertension(PH) is a progressive disease with a high morbidity and mortality rate; and neointima formation leads to the irreversibility of the disease.We have previously reported that in rats, monocrotaline(MCT) injection leads to progressive disruption of endothelial cells(EC), and endothelial caveolin-1(cav-1) loss, accompanied by the activation of pro-proliferative pathways leading to PH. Four weeks post-MCT, extensive endothelial cav-1 loss is associated with increased cav-1 expression in smooth muscle cells(SMC). Exposing the MCTtreated rats to hypoxia hastens the disease process; and at 4 wk, neointimal lesions and occlusion of the small arteries are observed.AIM To identify the alterations that occur during the progression of PH that lead to neointima formation.METHODS Male Sprague-Dawley rats(150-175 g) were divided in 4 groups(n = 6-8 per group): controls(C); MCT(M, a single sc injection 40 mg/kg); Hypoxia(H,hypobaric hypoxia); MCT + hypoxia(M+H, MCT-injected rats subjected to hypobaric hypoxia starting on day1). Four weeks later, right ventricular systolic pressure(RVSP), right ventricular hypertrophy(RVH), lung histology, and cav-1 localization using immunofluorescence technique were analyzed. In addition, the expression of cav-1, tyrosine 14 phosphorylated cav-1(p-cav-1), caveolin-2(cav-2), cavin-1, vascular endothelial cadherin(VE-Cad) and p-ERK1/2 in the lungs were examined, and the results were compared with the controls.RESULTSSignificant PH and right ventricular hypertrophy were present in M and H groups [RVSP, mmHg, M 54±5~*, H 45±2~*, vs C 20±1, P < 0.05; RVH, RV/LV ratio M 0.57±0.02~*, H 0.50±0.03~*, vs C 0.23±0.007, P < 0.05]; with a further increase in M+H group [RVSP 69±9 mmHg, RV/LV 0.59±0.01 P < 0.05 vs M and H]. All experimental groups revealed medial hypertrophy; but only M+H group exhibited small occluded arteries and neointimal lesions. Immunofluorescence studies revealed endothelial cav-1 loss and increased cav-1 expression in SMC in M group; however, thBACKGROUND Pulmonary hypertension(PH) is a progressive disease with a high morbidity and mortality rate; and neointima formation leads to the irreversibility of the disease.We have previously reported that in rats, monocrotaline(MCT) injection leads to progressive disruption of endothelial cells(EC), and endothelial caveolin-1(cav-1) loss, accompanied by the activation of pro-proliferative pathways leading to PH. Four weeks post-MCT, extensive endothelial cav-1 loss is associated with increased cav-1 expression in smooth muscle cells(SMC). Exposing the MCTtreated rats to hypoxia hastens the disease process; and at 4 wk, neointimal lesions and occlusion of the small arteries are observed.AIM To identify the alterations that occur during the progression of PH that lead to neointima formation.METHODS Male Sprague-Dawley rats(150-175 g) were divided in 4 groups(n = 6-8 per group): controls(C); MCT(M, a single sc injection 40 mg/kg); Hypoxia(H,hypobaric hypoxia); MCT + hypoxia(M+H, MCT-injected rats subjected to hypobaric hypoxia starting on day1). Four weeks later, right ventricular systolic pressure(RVSP), right ventricular hypertrophy(RVH), lung histology, and cav-1 localization using immunofluorescence technique were analyzed. In addition, the expression of cav-1, tyrosine 14 phosphorylated cav-1(p-cav-1), caveolin-2(cav-2), cavin-1, vascular endothelial cadherin(VE-Cad) and p-ERK1/2 in the lungs were examined, and the results were compared with the controls.RESULTSSignificant PH and right ventricular hypertrophy were present in M and H groups [RVSP, mmHg, M 54±5~*, H 45±2~*, vs C 20±1, P < 0.05; RVH, RV/LV ratio M 0.57±0.02~*, H 0.50±0.03~*, vs C 0.23±0.007, P < 0.05]; with a further increase in M+H group [RVSP 69±9 mmHg, RV/LV 0.59±0.01 P < 0.05 vs M and H]. All experimental groups revealed medial hypertrophy; but only M+H group exhibited small occluded arteries and neointimal lesions. Immunofluorescence studies revealed endothelial cav-1 loss and increased cav-1 expression in SMC in M group; however, th

关 键 词：CAVEOLIN-1 Cavin-1 NEOINTIMA Phospho-caveolin1 PULMONARY HYPERTENSION 

分 类 号：R[医药卫生]