Angiotensin type 2-receptor (AT2R) activation induces hypotension in apolipoprotein E-deficient mice by activating peroxisome proliferator-activated receptor-γ

科研成果详情

题名	Angiotensin type 2-receptor (AT2R) activation induces hypotension in apolipoprotein E-deficient mice by activating peroxisome proliferator-activated receptor-γ
作者	Li, Ming 1,6; Tejada, Thor 1; Lambert, Jonathan P.3; Nicholson, Chad K.3; Yahiro, Eiji 1; Ambai, Vats T.1; Ali, Syeda F.1; Bradley, Eddie W.4; Graham, Robert M.2; Dell'Italia, Louis J.4,5; Calvert, John W.3; Naqvi, Nawazish 1
发表日期	2016
发表期刊	AMERICAN JOURNAL OF CARDIOVASCULAR DISEASE 影响因子和分区
语种	英语
原始文献类型	Article
关键词	AT(2)R apoE((-/-)) angiotensin II blood pressure eNOS PPAR-gamma
其他关键词	NITRIC-OXIDE SYNTHASE ; ISCHEMIA-REPERFUSION ; SUBTYPES ; CELLS ; RAT ; ATHEROSCLEROSIS ; EXPRESSION ; PROTECTS ; TISSUES ; LESIONS
摘要	Angiotensin II (Ang II) modulates blood pressure and atherosclerosis development through its vascular type-1 (AT(1)R) and type-2 (AT(2)R) receptors, which have opposing effects. AT(2)R activation produces hypotension, and is anti-atherogenic. Targeted overexpression of AT(2)Rs in vascular smooth muscle cells (VSMCs) indicates that these effects are due to increased nitric oxide (NO) generation. However, the role of endogenous VSMC AT(2)Rs in these events is unknown. Effect of 7-day low-dose Ang II-infusion (12 mu g/kg/hr) on blood pressure was tested in 9-week-old apoE((-/-)) mice fed a low or high cholesterol diet (LCD or HCD, respectively). Cardiac output was measured by echo-cardiography. Immunohistochemistry was performed to localize and quantify AT(2)Rs and p-Ser(1177)-endothelial nitric oxide synthase (eNOS) levels in the aortic arch. PD123319 and GW-9662 were used to selectively block the AT(2)R and peroxisome proliferator-activated receptor-gamma (PPAR-gamma), respectively. Ang II infusion decreased blood pressure by 12 mmHg (P < 0.001) in LCD/apoE((-/-)) mice without altering cardiac output; a response blocked by PD123319. Although, AT(2)R stimulation neither activated eNOS (p-Ser(1177)-eNOS) nor changed plasma NO metabolites, it caused an similar to 6-fold increase in VSMC PPAR-gamma levels (P < 0.001) and the AT(2)R-mediated hypotension was abolished by GW-9662. AT(2)R-mediated hypotension was also inhibited by HCD, which selectively decreased VSMC AT(2)R expression by similar to 6-fold (P < 0.01). These findings suggest a novel pathway for the Ang II/AT(2)R-mediated hypotensive response that involves PPAR-gamma, and is down regulated by a HCD.
资助项目	Department of Medicine, Emory University; Carlyle Fraser Heart Center, Emory University Hospital Midtown; NIH [NIH 1RO1HL127726-01A1, HL079040, HL127726, 5R01HL098481-05]; American Heart Association [13SDG16460006]; National Health and Medical Research Council of Australia [573732]; public welfare of science and technology grants; city bureau of finance in science and technology of Wenzhou, China [Y20140671]
出版者	E-CENTURY PUBLISHING CORP
ISSN	2160-200X
卷号	6 期号:3 页码:118-128
页数	11
WOS类目	Cardiac & Cardiovascular Systems
WOS研究方向	Cardiovascular System & Cardiology
WOS记录号	WOS:000384819900005
收录类别	ESCI
Pubmed记录号	27679746
通讯作者地址	[Naqvi, Nawazish]Emory Univ, Cardiol, 101 Woodruff Circle NE, Atlanta, GA 30322 USA.
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/213274
专题	基础医学院（机能实验教学中心）_基础医学研究中心_心脏再生医学研究所
通讯作者	Naqvi, Nawazish
作者单位	1.Emory Univ, Dept Med, Div Cardiol, 101 Woodruff Circle NE, Atlanta, GA 30322 USA; 2.Victor Chang Cardiac Res Inst, Darlinghurst, NSW 2010, Australia; 3.Emory Univ, Dept Surg, Carlyle Fraser Heart Ctr, Div Cardiothorac Surg, 101 Woodruff Circle NE, Atlanta, GA 30322 USA; 4.Univ Alabama Birmingham, Dept Med, Birmingham, AL 35294 USA; 5.VA Med Ctr, Birmingham, AL USA; 6.Wenzhou Med Univ, Cardiac Regenerat Res Inst, Wenzhou 325035, Peoples R China
第一作者单位	温州医科大学
推荐引用方式 GB/T 7714	Li, Ming,Tejada, Thor,Lambert, Jonathan P.,et al. Angiotensin type 2-receptor (AT2R) activation induces hypotension in apolipoprotein E-deficient mice by activating peroxisome proliferator-activated receptor-γ[J]. AMERICAN JOURNAL OF CARDIOVASCULAR DISEASE,2016,6(3):118-128.
APA	Li, Ming., Tejada, Thor., Lambert, Jonathan P.., Nicholson, Chad K.., Yahiro, Eiji., ... & Naqvi, Nawazish. (2016). Angiotensin type 2-receptor (AT2R) activation induces hypotension in apolipoprotein E-deficient mice by activating peroxisome proliferator-activated receptor-γ. AMERICAN JOURNAL OF CARDIOVASCULAR DISEASE, 6(3), 118-128.
MLA	Li, Ming,et al."Angiotensin type 2-receptor (AT2R) activation induces hypotension in apolipoprotein E-deficient mice by activating peroxisome proliferator-activated receptor-γ".AMERICAN JOURNAL OF CARDIOVASCULAR DISEASE 6.3(2016):118-128.