Anhui Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, P.R. China.
Department of Cardiac surgery, The First Affiliated Hospital of Bengbu Medical College, Bengbu, P.R. China.
Cell Transplant. 2022 Jan-Dec;31:9636897221081479. doi: 10.1177/09636897221081479.
Pulmonary arterial hypertension (PAH) is a disease that plagues a major portion of the world's population, and there is currently no effective cure for this ailment. The proliferation and migration of pulmonary artery smooth muscle cells (PASMC) are known to be the pathological basis of pulmonary vascular remodeling in pulmonary hypertension. Studies in the past have shown involvement of CircRNA in the pathology of pulmonary as well as cardiovascular diseases. However, there are very few studies that have analyzed the relationship between CircRNA and PAH. The aim of this study was to explore this relationship by using rat PAH model. A hypoxic, PAH rat model was constructed for this study and the subsequently produced hypoxia-induced rat PASMC cells were utilized to demonstrate the reduction in expression of circular RNA of Silent information regulator factor 2-related enzyme 1 (circ-Sirt1) and SIRT1 mRNA in response to hypoxia, through cell function tests, cell rescue tests, and physical tests. We found that the expression of circ-Sirt1 and SIRT1 decreased in the PAH rat model induced by hypoxia. It was also revealed that the overexpression of circ-SIRT1 increased SIRT1 levels, but inhibited the expression of transforming growth factor (TGF)-β1, Smad3, and Smad7, and weakened PASMC cell vitality, proliferation, and migration ability. The findings of the present study indicate that circ-Sirt1 regulates the expression of SIRT1 mRNA and inhibits TGF-β1/Smad3/Smad7 mediated proliferation and migration of PASMC. This provides a new insight into the molecular mechanism of pulmonary artery vascular remodeling in PAH and may aid in the development of novel therapeutic options for management of PAH.
肺动脉高压（PAH）是一种困扰世界大部分人口的疾病，目前尚无有效的治疗方法。肺动脉平滑肌细胞（PASMC）的增殖和迁移被认为是肺动脉高压肺血管重构的病理基础。过去的研究表明，CircRNA 参与了肺和心血管疾病的病理过程。然而，目前关于 CircRNA 与 PAH 之间关系的研究非常少。本研究旨在通过使用大鼠 PAH 模型来探讨这种关系。本研究构建了缺氧性 PAH 大鼠模型，并利用随后产生的缺氧诱导的大鼠 PASMC 细胞，通过细胞功能试验、细胞拯救试验和物理试验，证明了沉默信息调节因子 2 相关酶 1（circ-Sirt1）的环状 RNA 和 SIRT1mRNA 的表达在缺氧条件下降低。我们发现，circ-Sirt1 和 SIRT1 的表达在缺氧诱导的 PAH 大鼠模型中降低。研究还表明，circ-Sirt1 的过表达增加了 SIRT1 水平，但抑制了转化生长因子（TGF）-β1、Smad3 和 Smad7 的表达，并减弱了 PASMC 细胞活力、增殖和迁移能力。本研究的结果表明，circ-Sirt1 调节 SIRT1mRNA 的表达，并抑制 TGF-β1/Smad3/Smad7 介导的 PASMC 增殖和迁移。这为 PAH 中肺动脉血管重构的分子机制提供了新的见解，并可能有助于开发治疗 PAH 的新治疗方法。
