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IR@PKUHSC  > 北京大学第三临床医学院  > 心血管内科  > 期刊论文
学科主题: 临床医学
题名:
Diverse Regulation of Cardiac Expression of Relaxin Receptor by alpha(1)- and beta(1)-Adrenoceptors
作者: 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
发表日期: 2014-06-01
DOI: 10.1007/s10557-014-6525-x
卷: 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
所属项目编号: 1004235 ; 1005329 ; 30910103902
项目资助者: National Health and Medical Research Council (NHMRC) ; Victorian Government&prime ; s Operational Infrastructure Program ; Nature Science Fund of China
WOS记录号: WOS:000338639900005
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/58534
Appears in Collections:北京大学第三临床医学院_心血管内科_期刊论文

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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

Recommended Citation:
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.
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