Medical Research Center, Beijing Chao-Yang Hospital, Capital Medical University, Beijing 100020, China.
Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Institute of Respiratory Medicine, Beijing 100020, China.
Biomed Res Int. 2018 Sep 18;2018:4892349. doi: 10.1155/2018/4892349. eCollection 2018.
This study aimed to explore whether bone marrow- (BM-) derived endothelial progenitor cells (EPCs) contributing to monocrotaline- (MCT-) induced pulmonary arterial hypertension (PAH) in rats via modulating store-operated Ca channels (SOC).
Sprague Dawley (SD) rats were assigned into MCT group (n = 30) and control group (n = 20). Rats in MCT group were subcutaneously administered with 60 mg/kg MCT solution, and rats in control group were injected with equal amount of vehicle. After 3 weeks of treatment, right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) of two groups were measured, and BM-derived EPCs were isolated. Immunochemistry identification and vasculogenesis detection of EPCs were then performed. [Ca] measurement was performed to detect store-operated calcium entry (SOCE) in two groups, followed by determination of Orai and canonical transient receptor potential (TRPC) channels expression.
After 3 weeks of treatment, there were significant increases in RVSP and RVHI in MCT group compared with control group, indicating that MCT successfully induced PAH in rats. Moreover, the SOCE ([Ca] rise) in BM-derived EPCs of MCT group was lower than that of control group. Furthermore, the expression levels of Orai3, TRPC1, TRPC3, and TRPC6 in BM-derived EPCs were decreased in MCT group in comparison with control group.
The SOC activities were inhibited in BM-derived EPCs of MCT-treated rats. These results may be associated with the depressed expression of Orai3, TRPC1, TRPC3, and TRPC6, which are major mediators of SOC.
本研究旨在探讨骨髓源性内皮祖细胞（EPCs）是否通过调节储存操纵钙通道（SOC）参与到大鼠 monocrotaline（MCT）诱导的肺动脉高压（PAH）中。
将 Sprague Dawley（SD）大鼠分为 MCT 组（n=30）和对照组（n=20）。MCT 组大鼠皮下给予 60mg/kg MCT 溶液，对照组大鼠注射等量溶剂。治疗 3 周后，测量两组大鼠的右心室收缩压（RVSP）和右心室肥厚指数（RVHI），分离骨髓源性 EPCs。然后进行 EPCs 的免疫化学鉴定和血管生成检测。测量两组细胞的[Ca]以检测 SOC 钙内流（SOCE），然后测定 Orai 和经典瞬时受体电位（TRPC）通道的表达。
治疗 3 周后，MCT 组大鼠的 RVSP 和 RVHI 均明显高于对照组，表明 MCT 成功诱导了大鼠的 PAH。此外，MCT 组 BM 源性 EPCs 的 SOCE（[Ca]升高）低于对照组。进一步的研究发现，与对照组相比，MCT 组 BM 源性 EPCs 中 Orai3、TRPC1、TRPC3 和 TRPC6 的表达水平降低。
MCT 处理的大鼠 BM 源性 EPCs 中的 SOC 活性受到抑制。这些结果可能与 SOC 的主要介质 Orai3、TRPC1、TRPC3 和 TRPC6 的表达下调有关。
