Mao Yuanjie, Su Jialin, Lei Lei, Meng Lei, Qi Yongfen, Huo Yong, Tang Chaoshu
aDepartment of Cardiology, Peking University First Hospital, Beijing, China bDepartment of Biochemistry, National Cerebral and Cardiovascular Center, Osaka, Japan cCardiology Division, Cardiovascular Research Center, Rhode Island Hospital and Alpert Medical School of Brown University, Providence, Rhode Island, USA dDepartment of Endocrinology, Beijing Aerospace Center Hospital eDepartment of Physiology, School of Basic Medical Sciences, Peking University, Beijing, China.
J Cardiovasc Med (Hagerstown). 2014 Jul;15(7):572-8. doi: 10.2459/JCM.0b013e3283629c30.
The activation of Gq-protein-coupled receptors induces proliferation of vascular smooth muscle cells (VSMCs) proliferation and is involved in vascular remodeling. The regulator of G protein signaling 2 (RGS2), which accelerates the termination of Gq protein signaling, may play a role in vascular remodeling. However, this role remains unclear.
Aortic balloon injury or sham operation was produced in male Wistar rats. Histological examination and gene expression analysis were performed after surgery. In cultured VSMCs after modulation of RGS2 expression, cell proliferation was also evaluated.
At day 3 after injury, RGS2 transcription was reduced by 52.8% (P <0.05 vs. sham group) with vascular remodeling. In cultured VSMCs stimulated by endothelin-1, phenylephrine or angiotensin II, the proliferation of RGS2 overexpressed cells was significantly inhibited; the proliferation of RGS2 downregulated cells was significantly promoted, compared with that of RGS2 normal cells. Moreover, after incubation with angiotensin II of high concentration (>10 μmol/l) or long term (>8 h), the RGS2 expression was clearly downregulated in cultured VSMCs. Administration of an angiotensin receptor blocker, valsartan (20 mg/kg per day) starting from 1 week preballoon injury to 3 days after injury, restored aortic RGS2 transcription and improved vascular remodeling.
These results suggested that the inhibiting effect of RGS2 on VSMC proliferation is downregulated in vascular remodeling of injured rat aorta, and this effect is likely to be mediated by angiotensin II signaling.
Gq蛋白偶联受体的激活可诱导血管平滑肌细胞（VSMC）增殖，并参与血管重塑。G蛋白信号调节因子2（RGS2）可加速Gq蛋白信号的终止，可能在血管重塑中发挥作用。然而，这一作用仍不明确。
对雄性Wistar大鼠进行主动脉球囊损伤或假手术。术后进行组织学检查和基因表达分析。在调节RGS2表达后的培养VSMC中，也评估细胞增殖情况。
损伤后第3天，随着血管重塑，RGS2转录降低了52.8%（与假手术组相比，P<0.05）。在内皮素-1、去氧肾上腺素或血管紧张素II刺激的培养VSMC中，RGS2过表达细胞的增殖受到显著抑制；与RGS2正常细胞相比，RGS2下调细胞的增殖显著促进。此外，在高浓度（>10μmol/L）或长期（>8小时）血管紧张素II孵育后，培养的VSMC中RGS2表达明显下调。从球囊损伤前1周开始至损伤后3天给予血管紧张素受体阻滞剂缬沙坦（每天20mg/kg），可恢复主动脉RGS2转录并改善血管重塑。
这些结果表明，在损伤大鼠主动脉的血管重塑中，RGS2对VSMC增殖的抑制作用下调，且这种作用可能由血管紧张素II信号介导。
