吴剑,邹云增

• 1:复旦大学附属中山医院上海市心血管病研究所

摘要(Abstract)：

<正>肾素-血管紧张素系统(RAS)中的所有成分如血管紧张素原、肾素、血管紧张素转换酶(ACE)及血管紧张素Ⅱ1型受体(AT1)在循环和组织(如心脏、肾脏)中均有发现,是心血管功能调节的一个重要系统,在维持血压和水电解质的内环境稳定上起着极其重要的作用。ACE2是2000年始有报道的RAS成员,可降解ACE的水解产物,与

关键词(KeyWords)：

Abstract:

Keywords:

基金项目(Foundation): 国家自然科学基金(81220108003;81200086);; 上海市科委基础处研究项目(11JC1402400;12ZR1442100);; 高等学校博士学科点专项科研基金(20110071110051;20120071120057)

作者(Author): 吴剑,邹云增

参考文献(References)：

• [1]Sadoshima J,Xu Y,Slayter HS,et al.Autocrine release of angiotensinⅡmediates stretch-induced hypertrophy of cardiac myocytes in vitro[J].Cell,1993,75(5):977-984.
• [2]Kudoh S,Komuro I,Mizuno T,et al.AngiotensinⅡstimulates c-Jun NH2-terminal kinase in cultured cardiac myocytes of neonatal rats[J].Circ Res,1997,80(1):139-146.
• [3]Harada K,KomuroⅠ,Hayashi D,et al.AngiotensinⅡtype la recetporr is involved in the occurrence of reperfusion arr-hythmias[J].Circulation,1998,97(4):315-317.
• [4]Zou Y,Akazawa H,Qin Y,et al.Mechanical stress activates angiotensinⅡtype1receptor without the involvement of an-giotensinⅡ[J].Nat Cell Biol,2004,6(6):499-506.
• [5]Zhou N,Li L,Wu J,et al.Mechanical stress-evoked but an-giotensinⅡ-independent activation of angiotensinⅡtype 1receptor induces cardiac hypertrophy through calcineurin pathway[J].Biochem Biophys Res Commun,2010,397(2):263-269.
• [6]You J,Wu J,Jiang G,et al.Olmesartan Attenuates cardiac re-modeling through DLL4/Notch1pathway activation in pressure overload mice[J].J Cardiovasc Pharmacol,2013,61(2):142-151.
• [7]Sano M,Minamino T,Toko H,et al.p53-induced inhibition of Hif-1causes cardiac dysfunction during pressure overload[J].Nature,2007,446(7134):444-448.
• [8]Rajagopal K,Whalen EJ,Violin JD,et al.Beta-arrestin2-mediated inotropic effects of the angiotensinⅡtype1A receptor in isolated cardiac myocytes[J].Proc Natl Acad Sci U S A,2006,103(44):16284-16289.
• [9]Rakesh K,Yoo B,Kim IM,et al.Beta-Arrestin-biased agonism of the angiotensin receptor induced by mechanical stress[J].Sci Signal,2010,3(125):ra46.
• [10]Kim KS,Abraham D,Williams B,et al.β-Arrestin-biased AT1R stimulation promotes cell survival during acute cardiac injury[J].Am J Physiol Heart Circ Physiol,2012,303(8):H1001-H1010.
• [11]Vickers C,Hales P,Kaushik V,et al.Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase[J].J Biol Chem,2002,277(17):14838-14843.
• [12]Crackower MA,Sarao R,Oudit GY,et al.Angiotensin-converting enzyme2is an essential regulator of heartfunction[J].Nature,2002,417(6891):822-828.
• [13]Yamamoto K,Ohishi M,Katsuya T,et al.Deletion of angio-tensin-converting enzyme2accelerates pressure overload-induced cardiac dysfunction by increasing local angiotensinⅡ[J].Hypertension,2006,47(4):718-726.
• [14]Der Sarkissian S,Grobe JL,Yuan L,et al.Cardiac overex-pression of angiotensin converting enzyme2protects the heart from ischemia-induced pathophysiology[J].Hypertension,2008,51(3):712-718.
• [15]Dong B,Yu QT,Dai HY,et al.Angiotensin-converting enzy-me-2overexpression improves left ventricular remodeling and function in a rat model of diabetic cardiomyopathy[J].J Am Coll Cardiol,2012,59(8):739-747.
• [16]Zhong J,Basu R,Guo D,et al.Angiotensin-converting enzyme 2suppresses pathological hypertrophy,myocardial fibrosis,and cardiac dysfunction[J].Circulation,2010,122(7):717-728.
• [17]Durik M,van Veghel R,Kuipers A,et al.The effect of the thioether-bridged,stabilized Angiotensin-(1-7)analogue cyclic ang-(1-7)on cardiac remodeling and endothelial function in rats with myocardial infarction[J].Int J Hypertens,2012,2012:536426.
• [18]Flores-Munoz M,Godinho BM,Almalik A,et al.Adenoviral delivery of angiotensin-(1-7)or angiotensin-(1-9)inhibits cardiomyocyte hypertrophy via the mas or angiotensin type2 receptor[J].PLoS One,2012,7(9):e45564.
• [19]Tallant EA,Ferrario CM,Gallagher PE.Angiotensin-(1-7)inhibits growth of cardiac myocytes through activation of the mas receptor[J].Am J Physiol Heart Circ Physiol,2005,289(4):H1560-H1566.
• [20]Santos RA,Castro CH,Gava E,et al.Impairment of in vitro and in vivo heart function in angiotensin-(1-7)receptor MAS knockout mice[J].Hypertension,2006,47(5):996-1002.
• [21]Botelho-Santos GA,Bader M,Alenina N,et al.Altered regional blood flow distribution in Mas-deficient mice[J].Therapeutic advances in cardiovascular disease,2012,6(5):201-211.
• [22]Jawien J,Toton-Zuranska J,Gajda M,et al.Angiotensin-(1-7)receptor Mas agonist ameliorates progress of atherosclerosis in apoE-knockout mice[J].J Physiol Pharmacol,2012,63(1):77-85.
• [23]Savergnini SQ,Beiman M,Lautner RQ,et al.Vascular relaxation,antihypertensive effect,and cardioprotection of a novel peptide agonist of the MAS receptor[J].Hypertension,2010,56(1):112-120.
• [24]Kaiqiang J,Minakawa M,Fukui K,et al.Olmesartan improves left ventricular function in pressure-overload hypertrophied rat heart by blocking angiotensinⅡreceptor with synergic effects of upregulation of angiotensin converting enzyme2[J].Ther Adv Cardiovasc Dis,2009,3(2):103-111.
• [25]Ishiyama Y,Gallagher PE,Averill DB,et al.Upregulation of angiotensin-converting enzyme2after myocardial infarction by blockade of angiotensinⅡreceptors[J].Hypertension,2004,43(5):970-976.
• [26]Kostenis E,Milligan G,Christopoulos A,et al.G-protein–coupled receptor Mas is a physiological antagonist ofthe angiotensinⅡtype1receptor[J].Circulation,2005,111(14):1806-1813.
• [27]Singh Y,Singh K,Sharma PL.Effect of combination of renin inhibitor and Mas-receptor agonist in DOCA-salt-induced hypertension in rats[J].Mol Cell Biochem,2013,373(1-2):189-194.
• [28]Gurley SB,Allred A,Le TH,et al.Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice[J].J Clin Invest,2006,116(8):2218-2225.
• [29]Wang W,Bodiga S,Das SK,et al.Role of ACE2in diastolic and systolic heart failure[J].Heart failure reviews,2012,17(4-5):683-691.
• [30]Yasuda N,Miura S,Akazawa H,et al.Conformational switch of angiotensinⅡtype1receptor underlying mechanical stress-induced activation[J].EMBO Rep,2008,9(2):179-186.
• [31]Li L,Zhou N,Gong H,et al.Comparison of angiotensinⅡtype1-receptor blockers to regress pressure overload-induced cardiac hypertrophy in mice[J].Hypertens Res,2010,33(12):1289-1297.
• [32]Miura S,Kiya Y,Hanzawa H,et al.Small molecules with similar structures exhibit agonist,neutral antagonist or inverse agonist activity toward angiotensinⅡtype1receptor[J].PLoS One,2012,7(6):e37974.
• [33]Hostrup A,Christensen GL,Bentzen BH,et al.Functionally selective AT(1)receptor activation reduces ischemia reperfusion injury[J].Cell Physiol Biochem,2012,30(3):642-652.