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| 同型半胱氨酸在大鼠血管平滑肌细胞上通过激活ERK1/2信号通路促进血管紧张素Ⅱ受体1表达 |
| 姜衡1△,于曼丽2△,魏勇1,欧阳平1,梁春3,吴宗贵3* |
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(1. 上海交通大学附属第一人民医院松江分院心内科, 上海 201600;
2. 第二军医大学长海医院心内科, 上海 200433;
3. 第二军医大学长征医院心内科, 上海 200003
△共同第一作者
*通信作者) |
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| 摘要: |
| 目的 观察同型半胱氨酸（homocysteine，Hcy）对大鼠血管平滑肌细胞（vascular smooth muscle cells，VSMCs）血管紧张素Ⅱ受体1（angiotensin Ⅱ receptor type 1，AT1R）蛋白表达的影响。方法 从大鼠胸主动脉分离、培养VSMCs，并用平滑肌特异性肌纤蛋白（α-SMA）进行免疫荧光鉴定；用10、100和300 μmol/L 3个不同浓度的Hcy孵育VSMCs，或在加入Hcy的同时加入5 μmol/L的ERK1/2通路阻断剂U0126，48 h后用免疫印迹法检测磷酸化的ERK1/2及AT1R的蛋白表达。结果 经鉴定，成功分离、培养VSMCs。10、100和300 μmol/L 3个不同浓度的Hcy均可上调VSMC的AT1R蛋白表达量（与溶剂对照组比较，P<0.05）。但3个浓度的Hcy组间差异无统计学意义（P>0.05）。10 μmol/L的Hcy可增加VSMC的ERK1/2磷酸化（P<0.05），激活ERK1/2信号通路。ERK1/2通路抑制剂U0126可完全阻断Hcy导致的ERK1/2磷酸化，并取消Hcy导致的AT1R上调。结论 Hcy可通过激活ERK1/2信号通路促进大鼠VSMC AT1R的表达，这一结果可能有助于揭示高Hcy血症与高血压的内在联系。 |
| 关键词: 高血压 同型半胱氨酸 血管平滑肌细胞 ERK1/2 血管紧张素Ⅱ受体1 |
| DOI：10.3724/SP.J.1008.2014.00968 |
| 投稿时间：2014-04-01修订日期：2014-05-29 |
| 基金项目:上海市松江区科委科学技术攻关项目（12SJGGYY02）. |
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| Homocysteine upregulates angiotensin Ⅱ receptor type 1 (AT1R) expression via activating ERK1/2 signaling pathway in rat vascular smooth muscle cells |
| JIANG Heng1△,YU Man-li2△,WEI Yong1,OUYANG Ping1,LIANG Chun3,WU Zong-gui3* |
(1. Department of Cardiology, The First People's Hospital of Shanghai(Songjiang Branch), Shanghai Jiaotong University, Shanghai 201600, China;
2. Department of Cardiology, Changhai Hospital, Second Military Medical University, Shanghai 200433, China;
3. Department of Cardiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
△Co-first authors.
* Corresponding author.) |
| Abstract: |
| Objective To study the influence of homocysteine on the protein expression of angiotensin Ⅱ receptor type 1 (AT1R) in rat vascular smooth muscle cells (VSMCs). Methods Primary rat VSMCs were isolated and cultured in vitro and identified by detecting α-SMA expression with immunofluorescence technique. VSMCs were exposed to three different concentrations of homocysteine (10, 100 and 300 μmol/L) alone or in combination with U0126 (5 μmol/L, a potent inhibitor of ERK1/2) for 48 h, and then immunoblotting method was used to detect AT1R protein expression and phosphorylation of ERK1/2. Results Primary rat VSMCs (positive for α-smooth muscle actin [α-SMA] staining) were isolated and cultured successfully. All the three different concentrations of homocysteine (10, 100 and 300 μmol/L) induced significant AT1R protein expression (P<0.05 vs solvent control group) in VSMCs, but there was no significant difference between the three groups. Moreover, homocysteine at 10 μmol/L significantly activated phosphorylation of ERK1/2 in VSMCs (P<0.05 vs blank control). Supplement of U0126 not only blocked the phosphorylation of ERK1/2 induced by homocysteine, but also abolished homocysteine-induced upregulation of AT1R. Conclusion Our results in this study indicate that homocysteine can upregulate AT1R protein expression via activating ERK1/2 signaling pathway in rat VSMCs, which may help to illustrate the relation between Hcy and hypertension. |
| Key words: hypertension homocysteine vascular smooth muscle cells ERK1/2 signaling angiotensin Ⅱ receptor type 1 |
