血管紧张素转化酶基因转染协同厄贝沙坦下调血管紧张素1型受体的表达
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摘要
目的研究血管紧张素转化酶(ACE)2基因转染对血管平滑肌细胞(VSMC)血管紧张素Ⅱ1型受体(AT1R)表达的影响。方法用含有ACE2基因的质粒pm-ACE2转染VSMC,通过RT-PCR和Western印迹比较ACE2基因转染、血管紧张素Ⅱ(Ang)Ⅱ、厄贝沙坦不同干预因素对AT1R表达的影响。结果与对照组相比,AngⅡ使AT1R表达明显增加(P<0.05),ACE2转染和厄贝沙坦干预则使AT1R表达明显减低(P<0.05);ACE2转染和厄贝沙坦干预均能明显抑制由AngⅡ诱导的AT1R表达。不论有无AngⅡ干预,ACE2基因转染联合厄贝沙坦干预抑制AT1R表达作用较单用ACE2基因转染或厄贝沙坦干预明显增强(P<0.05)。结论 ACE2基因转染具有下调VSMC AT1R表达的作用,并且能与厄贝沙坦协同下调AT1R的表达。
引文
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12 赵三妹,夏人仪,乇宗立,等.动脉平滑肌细胞的培养方法及其应用[J].中华病理学杂志,1987;16(4):260-2.
13 Tikellis C,Bernardi S,Burns WC.Angiotensin-converting enzyme 2 is a key modulator of the renin-angiotensin system in cardiovascular and renal disease[J].Curr Opin Nephrol Hypertens,2011;20(1):62-8.
14 Oudit GY,Kassiri Z,Patel MP,et al.AngiotensinⅡ-mediated oxidative stress and inflammation mediate the age-dependent cardiomyopathy in ACE2 null mice[J].Cardiovasc Res,2007;75(1):29-39.
15 Zhao YX,Yin HQ,Yu QT,et al.ACE2 overexpression ameliorates left ventricular remodeling and dysfunction in a rat model of myocardial infarction[J].Hum Gene Ther,2010;21(11):1545-54.
16 Xiao L,Gao L,Lazartigues E,et al.Brain-selective overexpression of angiotensin-converting enzyme 2 attenuates sympathetic nerve activity and enhances baroreflex function in chronic heart failure[J].Hypertension,2011;58(6):1057-65.
17 Huang H,Zhou J,Cui Z,et al.AngiotensinⅡtype 1 receptor-associated protein plays a role in regulating the local renin-angiotensin system in HSC-T6 cells[J].Mol Med Rep,2015;12(3):3763-8.
18 Igase M,Kohara K,Nagai T,et al.Increased expression of angiotensin converting enzyme 2 in conjunction with reduction of neointima by angiotensinⅡtype 1 receptor blockade[J].Hypertens Res,2008;31(3):553-9.
19 Gallagher PE,Ferrario CM,Tallant EA.MAP kinase/phosphatase pathway mediates the regulation of ACE2 by angiotensin peptides[J].Am J Physiol Cell Physiol,2008;295:C1169-74.
2 Suzuki H,Motley ED,Frank GD,et al.Recent progress in signal transduction research of the angiotensinⅡtype-1 receptor:protein kinases,vascular dysfunction and structural requirement[J].Curr Med Chem Cardiovasc Hematol Agents,2005;3:305-22.
3 Mifune M,Ohtsu H,Suzuki H,et al.G protein coupling and second messenger generation are indispensable for metalloprotease-dependent,heparin binding epidermal growth factor shedding through angiotensinⅡtype-1 receptor[J].J Biol Chem,2005;280:26592-9.
4 Mendoza-Torres E,Oyarzún A,Mondaca-Ruff D,et al.ACE2 and vasoactive peptides:novel players in cardiovascular/renal remodeling and hypertension[J].Ther Adv Cardiovasc Dis,2015;9(4):217-37.
5 Katvich MJ,Grobe JL,Huentelman M,et al.Angiotensin-converting enzyme 2 as a novel taget for gene therapy for hypertension[J].Exp Physiol,2005;90:299-305.
6 Danilczyk U,Eriksson U,Oudit GY,et al.Physiological roles of angiotensin-converting enzyme 2[J].Cell Mol Life Sci,2004;61:2714-9.
7 Der Sarkissian S,Huentelman MJ,Stewart J,et al.ACE2:a novel therapeutic target for cardiovascular disease[J].Prog Biophys Mol Biol,2006;91:163-98.
8 Koka V,Huang XR,Chung ACK,et al.AngiotensinⅡup-regulates angiotensin converting enzyme(ACE),but down-regulates ACE2 via the AT1-ERK/p38 MAP kinase pathway[J].Am J Pathol,2008;172(5):1174-83.
9 Xia H,Feng Y,Obr TD,et al.AngⅡtype 1 receptor-mediated reduction of angiotensin-converting enzyme 2 activity in the brain impairs baroreflex fuction in hypertensive mice[J].Hypertension,2009;53:210-6.
10 晋学庆,卢卓强,林旭.血管紧张素转换酶2基因转染抑制平滑肌细胞增殖[J].中华医学杂志,2011;91(2):125-8.
11 卢卓强,晋学庆.小鼠血管紧张素转化酶2基因表达型载体的构建及体外表达[J].中国组织工程研究与临床康复,2010;14(46):8600-3.
12 赵三妹,夏人仪,乇宗立,等.动脉平滑肌细胞的培养方法及其应用[J].中华病理学杂志,1987;16(4):260-2.
13 Tikellis C,Bernardi S,Burns WC.Angiotensin-converting enzyme 2 is a key modulator of the renin-angiotensin system in cardiovascular and renal disease[J].Curr Opin Nephrol Hypertens,2011;20(1):62-8.
14 Oudit GY,Kassiri Z,Patel MP,et al.AngiotensinⅡ-mediated oxidative stress and inflammation mediate the age-dependent cardiomyopathy in ACE2 null mice[J].Cardiovasc Res,2007;75(1):29-39.
15 Zhao YX,Yin HQ,Yu QT,et al.ACE2 overexpression ameliorates left ventricular remodeling and dysfunction in a rat model of myocardial infarction[J].Hum Gene Ther,2010;21(11):1545-54.
16 Xiao L,Gao L,Lazartigues E,et al.Brain-selective overexpression of angiotensin-converting enzyme 2 attenuates sympathetic nerve activity and enhances baroreflex function in chronic heart failure[J].Hypertension,2011;58(6):1057-65.
17 Huang H,Zhou J,Cui Z,et al.AngiotensinⅡtype 1 receptor-associated protein plays a role in regulating the local renin-angiotensin system in HSC-T6 cells[J].Mol Med Rep,2015;12(3):3763-8.
18 Igase M,Kohara K,Nagai T,et al.Increased expression of angiotensin converting enzyme 2 in conjunction with reduction of neointima by angiotensinⅡtype 1 receptor blockade[J].Hypertens Res,2008;31(3):553-9.
19 Gallagher PE,Ferrario CM,Tallant EA.MAP kinase/phosphatase pathway mediates the regulation of ACE2 by angiotensin peptides[J].Am J Physiol Cell Physiol,2008;295:C1169-74.