Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University in Bratislava, Slovakia.
Centre of Experimental Medicine, Slovak Academy of Sciences, Institute of Normal and Pathological Physiology, Bratislava, Slovakia.
Clin Exp Hypertens. 2022 Feb 17;44(2):101-112. doi: 10.1080/10641963.2021.1996589. Epub 2021 Nov 7.
Caveolin-1 (cav-1) plays a role in pulmonary arterial hypertension (PAH). Monocrotaline (MCT)-induced PAH is characterized by a loss of cav-1 in pulmonary arteries; however, less is known regarding its role in the hypertrophied right ventricle (RV). We aimed to characterize the role of cav-1 and Hsp90 in the RV of MCT-induced PAH and their impact on endothelial nitric oxide synthase (eNOS). Additionally, we focused on restoration of cav-1 expression with pioglitazone administration.
Male 12-week-old Wistar rats were injected subcutaneously with monocrotaline (60 mg/kg). Selected proteins (cav-1, eNOS, pSer1177eNOS, Hsp90) and mRNAs (cav-1α, cav-1β, eNOS) were determined in the RV and left ventricle (LV) 4 weeks later. In a separate MCT-induced PAH study, pioglitazone (10 mg/kg/d, orally) administration started on day 14 after MCT.
MCT induced RV hypertrophy and lung enlargement. Cav-1 and pTyr14cav-1 were decreased in RV. Caveolin-1α (cav-1α) and caveolin-1β (cav-1β) mRNAs were decreased in both ventricles. Hsp90 protein was increased in RV. eNOS and pSer1177eNOS proteins were unchanged in the ventricles. eNOS mRNA was reduced in RV. Pioglitazone treatment increased oxygen saturation and pTyr14cav-1 vs. MCT group.
Restoration of pTyr14cav-1 did not lead to amelioration of the disease, nor did it prevent RV hypertrophy and fibrosis, which was indicated by an increase in Acta2, Nppb, Col3a1, and Tgfβ1 mRNA.
小窝蛋白-1（cav-1）在肺动脉高压（PAH）中起作用。野百合碱（MCT）诱导的 PAH 的特征是肺动脉中小窝蛋白-1 的丢失；然而，关于其在肥大的右心室（RV）中的作用知之甚少。我们旨在研究 cav-1 和热休克蛋白 90（Hsp90）在 MCT 诱导的 PAH 中的 RV 中的作用及其对内皮型一氧化氮合酶（eNOS）的影响。此外，我们专注于用吡格列酮给药恢复 cav-1 表达。
雄性 12 周龄 Wistar 大鼠皮下注射野百合碱（60mg/kg）。4 周后，测定 RV 和左心室（LV）中的选定蛋白（cav-1、eNOS、pSer1177eNOS、Hsp90）和 mRNA（cav-1α、cav-1β、eNOS）。在另一项 MCT 诱导的 PAH 研究中，吡格列酮（10mg/kg/d，口服）给药于 MCT 后第 14 天开始。
MCT 诱导 RV 肥大和肺增大。RV 中小窝蛋白-1（cav-1）和 pTyr14cav-1 减少。两种心室 cav-1α（cav-1α）和 cav-1β（cav-1β）mRNA 减少。Hsp90 蛋白在 RV 中增加。eNOS 和 pSer1177eNOS 蛋白在心室中不变。eNOS mRNA 在 RV 中减少。吡格列酮治疗可提高氧饱和度和 pTyr14cav-1 与 MCT 组相比。
恢复 pTyr14cav-1 并未改善疾病，也未能预防 RV 肥大和纤维化，这表明 Acta2、Nppb、Col3a1 和 Tgfβ1 mRNA 增加。
