Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
Department of Cadre, the First Affiliated Hospital of Harbin Medical University, Harbin, China.
Life Sci. 2020 Jul 15;253:117726. doi: 10.1016/j.lfs.2020.117726. Epub 2020 Apr 26.
Vascular smooth muscle cell (VSMC) proliferation plays a significant role in the development of various vascular disorders. However, the effect of cortistatin (CST) on VSMC proliferation remains unclear. Therefore, the purpose of our research aimed to study whether CST protected VSMCs from angiotensin II (Ang II)-induced proliferation and which mechanisms participated in the process.
Cultured rat VSMCs were treated with Ang II with or without CST for 24 h. Cell proliferation rate was measured by cell counting kit-8 (CCK8) assay. The expressions of CST and its receptors were assessed by quantitative real-time PCR (qRT-PCR). The protein expression levels were analyzed by western blots. Immunofluorescence and transmission electron microscopy (TEM) were used to observe autophagy.
Our results showed that different concentrations of CST alleviated the Ang II-induced VSMC proliferation. The autophagy and reactive oxygen species (ROS) stimulated by Ang II were attenuated by CST. Furthermore, when the autophagy inhibitor 3-methyladenine (3-MA) was added, it exerted similar inhibition effects like CST, but didn't augment the protective role of CST on Ang II-induced VSMC autophagy and proliferation. Moreover, blocking somatostatin receptor 3 and 5 (SSTR3 and SSTR5) partially abrogated the suppressive effect of CST on Ang II-stimulated VSMC proliferation and autophagy.
This study indicated that CST could ameliorate Ang II-stimulated VSMC proliferation by inhibiting autophagy partially through its receptors SSTR3 and SSTR5, providing a reasonable evidence for CST as a novel perspective therapeutic target of vascular diseases.
血管平滑肌细胞（VSMC）增殖在各种血管疾病的发展中起着重要作用。然而，Cortistatin（CST）对 VSMC 增殖的影响尚不清楚。因此，我们的研究旨在研究 CST 是否能保护 VSMCs 免受血管紧张素 II（Ang II）诱导的增殖，以及哪些机制参与了这一过程。
用 Ang II 和/或 CST 处理培养的大鼠 VSMCs 24 小时。通过细胞计数试剂盒-8（CCK8）测定细胞增殖率。通过定量实时 PCR（qRT-PCR）评估 CST 及其受体的表达。通过 Western blot 分析蛋白表达水平。免疫荧光和透射电子显微镜（TEM）用于观察自噬。
我们的结果表明，不同浓度的 CST 减轻了 Ang II 诱导的 VSMC 增殖。CST 减弱了 Ang II 刺激的自噬和活性氧（ROS）。此外，当添加自噬抑制剂 3-甲基腺嘌呤（3-MA）时，它发挥了与 CST 类似的抑制作用，但没有增强 CST 对 Ang II 诱导的 VSMC 自噬和增殖的保护作用。此外，阻断生长抑素受体 3 和 5（SSTR3 和 SSTR5）部分阻断了 CST 对 Ang II 刺激的 VSMC 增殖和自噬的抑制作用。
这项研究表明，CST 可以通过其受体 SSTR3 和 SSTR5 部分抑制自噬来减轻 Ang II 刺激的 VSMC 增殖，为 CST 作为血管疾病的一种新的治疗靶点提供了合理的证据。
