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Diverse Regulation of Cardiac Expression of Relaxin Receptor by alpha(1)- and beta(1)-Adrenoceptors
Moore, Xiao-Lei1; Su, Yidan1; Fan, Yingli1; Zhang, You-Yi3,4; Woodcock, Elizabeth A.1; Dart, Anthony M.1,2; Du, Xiao-Jun1,2
关键词Relaxin family peptide receptor-1 (RXFP1) Adrenoceptors Cardiomyocyte
刊名CARDIOVASCULAR DRUGS AND THERAPY
2014-06-01
DOI10.1007/s10557-014-6525-x
28期:3页:221-228
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Pharmacology & Pharmacy
研究领域[WOS]Cardiovascular System & Cardiology ; Pharmacology & Pharmacy
关键词[WOS]CONGESTIVE-HEART-FAILURE ; MYOCARDIAL-INFARCTION ; HYPERTENSIVE-RATS ; ACTIVATION ; HYPERTROPHY ; CARDIOMYOCYTES ; NOREPINEPHRINE ; SERELAXIN ; FIBROSIS ; ARRESTIN
英文摘要

Relaxin, a new drug for heart failure therapy, exerts its cardiac actions through relaxin family peptide receptor 1 (RXFP1). Factors regulating RXFP1 expression remain unknown. We have investigated effects of activation of adrenoceptors (AR), an important modulator in the development and prognosis of heart failure, on expression of RXFP1 in rat cardiomyocytes and mouse left ventricles (LV).

Expression of RXFP1 at mRNA (real-time PCR) and protein levels (immunoblotting) was measured in cardiomyocytes treated with alpha- and beta-AR agonists or antagonists. RXFP1 expression was also determined in the LV of transgenic mouse strains with cardiac-restricted overexpression of alpha(1A)-, alpha(1B)- or beta(2)-AR. Specific inhibitors were used to explore signal pathways involved in alpha(1)-AR mediated regulation of RXFP1 in cardiomyocytes.

In cultured cardiomyocytes, alpha(1)-AR stimulation resulted in 2-3 fold increase in RXFP1 mRNA (P < 0.001), which was blocked by specific inhibitors for protein kinase C (PKC) or mitogen-activated protein kinases/extracellular signal-regulated kinases (MAPK/ERK). Activation of beta(1)-, but not beta(2)-AR, significantly inhibited RXFP1 expression (P < 0.001). Relative to respective wild-type controls, RXFP1 mRNA levels in the LV of mice overexpressing alpha(1A)- or alpha(1B)-AR were increased by 3- or 10-fold, respectively, but unchanged in beta(2)-AR transgenic hearts. Upregulation by alpha(1)-AR stimulation RXFP1 expression was confirmed at protein levels both in vitro and in vivo.

Expression of RXFP1 was up-regulated by alpha(1)-AR but suppressed by beta-AR, mainly beta(1)-AR subtype, in cardiomyocytes. Future studies are warranted to characterize the functional significance of such regulation, especially in the setting of heart failure.

语种英语
WOS记录号WOS:000338639900005
项目编号1004235 ; 1005329 ; 30910103902
资助机构National Health and Medical Research Council (NHMRC) ; Victorian Government&prime ; s Operational Infrastructure Program ; Nature Science Fund of China
引用统计
被引频次:9[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58534
专题北京大学第三临床医学院_心血管内科
作者单位1.Monash Univ, Cent Clin Sch, Melbourne, Vic 3004, Australia
2.Peking Univ, Inst Vasc Med, Beijing 100871, Peoples R China
3.Peking Univ, Hosp 3, Beijing 100871, Peoples R China
4.Baker IDI Heart & Diabet Inst, Melbourne, Vic 3004, Australia
推荐引用方式
GB/T 7714
Moore, Xiao-Lei,Su, Yidan,Fan, Yingli,et al. Diverse Regulation of Cardiac Expression of Relaxin Receptor by alpha(1)- and beta(1)-Adrenoceptors[J]. CARDIOVASCULAR DRUGS AND THERAPY,2014,28(3):221-228.
APA Moore, Xiao-Lei.,Su, Yidan.,Fan, Yingli.,Zhang, You-Yi.,Woodcock, Elizabeth A..,...&Du, Xiao-Jun.(2014).Diverse Regulation of Cardiac Expression of Relaxin Receptor by alpha(1)- and beta(1)-Adrenoceptors.CARDIOVASCULAR DRUGS AND THERAPY,28(3),221-228.
MLA Moore, Xiao-Lei,et al."Diverse Regulation of Cardiac Expression of Relaxin Receptor by alpha(1)- and beta(1)-Adrenoceptors".CARDIOVASCULAR DRUGS AND THERAPY 28.3(2014):221-228.
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