PTEN抑制钙/钙调神经磷酸酶信号通路、负性调控血管紧张素Ⅱ所致心肌细胞肥大  

Angiotensin Ⅱ induced cardiac hypertrophy is blocked by PTEN via suppressing Ca^(2+)/Calcineurin pathway

作　　者：于林君[1] 祝善俊[1] 周裔忠[1] 王江[1] 田颖[1] 祝之明[2] 

机构地区：[1]第三军医大学新桥医院心内科 [2]第三军医大学大坪医院高血压科

出　　处：《中华心血管病杂志》2006年第6期541-545,共5页Chinese Journal of Cardiology

基　　金：国家自然科学基金资助项目(30370584)

摘　　要：目的观察PTEN过度表达对血管紧张素Ⅱ(AngⅡ)刺激所致钙/钙调神经磷酸酶(Ca2+/CaN)信号通路激活的影响,探讨PTEN负性调控心肌肥厚的作用机制。方法通过携带野生型PTEN基因的腺病毒(Ad-PTEN)感染构建过度表达PTEN的原代培养心肌细胞模型,用AngⅡ作为促心肌肥厚刺激剂,Fura-2/AM比率荧光成像系统检测细胞内Ca2+浓度([Ca2+]i),逆转录聚合酶链反应检测受感染细胞内心房利钠因子(ANF)、β-肌球蛋白重链(β-MHC)与CaNAβ的mRNA表达,Westernblot检测CaNAβ的蛋白表达,同时测定CaN活性。结果Ad-PTEN感染后,心肌细胞内过度表达PTEN的mRNA和蛋白。PTEN的过度表达能够明显抑制AngⅡ刺激所致的心肌细胞肥大标志基因表达。AngⅡ刺激使[Ca2+]i、CaNAβmRNA与蛋白表达以及CaN活性明显增高,PTEN过度表达能够明显抑制AngⅡ引起的[Ca2+]i、CaNAβmRNA与蛋白表达以及CaN活性增高。结论PTEN过度表达可能通过抑制Ca2+/CaN信号通路,负性调控AngⅡ刺激所致的心肌细胞肥大。Objective To investigate the effects of PTEN on AnglI induced cardiomyocyte hypertrophy and subsequent Ca^2＋/Calcineurin pathway changes. Methods Primary cultured neonatal rat cardiomyocytes were cultured and were treated with phosphate-buffered saline, empty adenovirus （Ad- GFP）, or adenovirus encoding for PTEN （Ad-PTEN-GFP） for 48 h and Ang Ⅱ （ 10^-7mol/L ） was added to the medium for another 24 h. Cells were harvested and intracellular Ca^2 ＋ concentration （ [ Ca^2 ＋ ] i ） was determined by Fura-2/AM ratio imaging analysis; PTEN, ANF, β-MHC and CaNAβ mRNA evaluated with RT-PCR; PTEN and CaNAβ protein by Western blot; CaN phosphatase activity by CaN detecting kits. Results PTEN at mRNA and protein levels were significantly higher in Ad-PTEN-GFP treated cardiomyocytes than that of Ad-GFP treated cardiomyocytes. Ang Ⅱ sitimulation upregulated [ Ca^2＋ ] i, CaNAβat mRNA and protein levels and CaN phosphatase activity in Ad-GFP treated cardiomyocytes but not in Ad-PTEN-GFP treated cardiomyocytes. Conclusions Cardiac hypertrophy induced by Ang Ⅱ could be blocked by PTEN overexpression via suppressing Ca^2＋/Calcineurin pathway.

关 键 词：心肌肥厚 钙 血管紧张素Ⅱ PTEN 钙调神经磷酸酶 

分 类 号：R541[医药卫生—心血管疾病]