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

• 作者: Jing Huang Rajamma Mathew
• 来源期刊: 世界高血压杂志
• 学科: 医学
• 关键词: CAVEOLIN-1 Cavin-1 NEOINTIMA Phospho-caveolin1 PULMONARY HYPERTENSION
• 年，卷（期）: 2019,（2）
• 页码范围: 17-29
• 页数: 13页
• 分类号: R

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. RESULTS Significant 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;