The renin-angiotensin system(RAS)regulates vascular tone and plays a critical role in vascular remodeling,which is the result of a complex interplay of alterations in vascular tone and structure.Inhibition of the RAS has led to important pharmacological tools to prevent and treat vascular diseases such as hypertension,diabetic vasculopathy and atherosclerosis.Angiotensin converting enzyme 2(ACE2)was recently identified as a multifunctional monocarboxypeptidase responsible for the conversion of angiotensin(Ang)II to Ang-(1-7).The ACE2/Ang-(1-7)signaling has been shown to prevent cellular proliferation,pathological hypertrophy,oxidative stress and vascular fibrosis.Thus,the ACE2/Ang-(1-7)signaling is deemed to be beneficial to the cardiovascular system as a negative regulator of the RAS.The addition of the ACE2/Ang-(1-7)signaling to the complexities of the RAS may lead to the development of novel therapeutics for the treatment of hypertension and other vascular diseases.The present review considers recent findings regarding the ACE2/Ang-(1-7)signaling and focuses on its regulatory roles in processes related to proliferation,inflammation,vascular fibrosis and remodeling,providing proof of principle for the potential use of ACE2 as a novel therapy for vascular disorders related to vascular remodeling.
ZHANG ZhenZhouCHEN LaiJiangZHONG JiuChangGAO PingJinOUDIT Gavin Y.
目的探讨替米沙坦干预对自发性高血压大鼠(SHR)血管组织血管紧张素转换酶2(ACE2)基因表达、一氧化氮(NO)及氧化应激水平的影响。方法选取10周龄SHR及其同源对照WKY大鼠,分别给予替米沙坦(5、10 mg.kg-1.d-1)或安慰剂,为期10周。采用Western blot检测治疗后大鼠主动脉组织中ACE2蛋白及内皮型NO合酶(eNOS)磷酸化水平。分别采用硝酸还原酶比色法与硫代巴比妥酸比色法测定大鼠主动脉组织中NO和丙二醛(MDA)含量。结果与WKY对照组相比,SHR大鼠主动脉组织中ACE2蛋白和Ser1177-eNOS磷酸化水平明显降低(ACE2:0.39±0.05vs 1.00±0.06;p-eNOS:0.43±0.06 vs 1.00±0.04;P值均<0.01),伴NO水平下调及MDA含量增加(NO mmol.g-1protein:11.5±2.1 vs 27.8±4.9;MDA nmol.g-1 protein:393.9±17.9 vs 186.3±14.5;P值均<0.01),而经替米沙坦治疗后SHR低、高剂量治疗组大鼠主动脉组织中ACE2蛋白和Ser1177-eNOS磷酸化水平增加(ACE2:0.62±0.06,0.65±0.07 vs 0.39±0.05;p-eNOS:0.68±0.07,0.71±0.06 vs0.43±0.06;P值均<0.05),伴NO水平升高(19.2±3.3,23.9±3.2 vs 11.5±2.1 mmol.g-1protein;P值均<0.05)与MDA含量下调(271.9±16.1,249.2±19.6 vs 393.9±17.9nmol.g-1protein;P值均<0.05)。结论长期替米沙坦治疗通过提升高血压大鼠血管ACE2表达及eNOS磷酸化水平,可促使血管NO生成及氧化应激水平改善,提示替米沙坦对高血压具有一定的血管保护功效。
