版权说明 帮助中心
首页 > 成果 > 详情

Intermedin Suppresses Pressure Overload Cardiac Hypertrophy through Activation of Autophagy

SCI-EMedline
WOS被引频次:45
认领
导出
Link by DOI
反馈
分享
QQ微信 微博
成果类型:
期刊论文
作者:
Chen, Huali;Wang, Xue;Tong, Mingming;Wu, Dan;Wu, Sisi;Chen, Jiaxiang;Wang, Xiaoxiao;Wang, Xulei;Kang, Yu;Tang, Hong;Tang, Chaoshu;Jiang, Wei*
通讯作者:
Jiang, Wei
作者机构:
[Wu, Sisi; Wang, Xue; Chen, Huali; Wang, Xulei; Jiang, Wei; Tong, Mingming; Wang, Xiaoxiao; Chen, Jiaxiang; Wu, Dan] Sichuan Univ, West China Hosp, Mol Med Res Ctr, State Key Lab Biotherapy, Chengdu 610064, Sichuan, Peoples R China.
[Wang, Xulei] Southwest Jiaotong Univ, Sch Life Sci & Bioengn, Chengdu, Sichuan, Peoples R China.
[Kang, Yu; Tang, Hong] Sichuan Univ, Dept Cardiol, West China Hosp, Chengdu 610064, Sichuan, Peoples R China.
[Kang, Yu] Chengdu Univ Tradit Chinese Med, Teaching Hosp, Chengdu, Sichuan, Peoples R China.
[Tang, Chaoshu] Peking Univ, Dept Physiol, Hlth Sci Ctr, Beijing 100871, Peoples R China.
通讯机构:
[Jiang, Wei] Sichuan Univ, West China Hosp, Mol Med Res Ctr, State Key Lab Biotherapy, Chengdu 610064, Sichuan, Peoples R China.
语种:
英文
关键词:
Autophagic cell death,Apoptosis,Heart,Cardiac hypertrophy,Surgical and invasive medical procedures,Brain natriuretic peptide,Analysis of variance,Cytoplasm
期刊:
PLOS ONE
ISSN:
1932-6203
年:
2013
卷:
8
期:
5
页码:
e64757
文献类别:
WOS:Article
所属学科:
ESI学科类别:临床医学;WOS学科类别:Multidisciplinary Sciences
入藏号:
基金类别:
National Natural Science Foundation of China [30871017, 31071001, 31271226, 81000056]; Key Projects in the Science and Technology Pillar Program of Sichuan Province [2009FZ0067]; National ST Major project [2012ZX09501001-003]
机构署名:
本校为其他机构
院系归属:
生命科学与工程学院
摘要:
Left ventricular hypertrophy is a maladaptive response to pressure overload and an important risk factor for heart failure. Intermedin (IMD), a multi-functional peptide, plays important roles in cardiovascular protection. In this study, we revealed an autophagy-dependent mechanism involved in IMD's protection against cardiac remodeling and cardiomyocyte death in heart hypertrophy. We observed that transverse aortic contraction (TAC) induction, Ang II or ISO exposure induced remarkable increase in the expression of endogenous IMD and its receptor components, CRLR, RAMP1 and RAMP3, in mouse hearts and H9c2 cell cultures, respectively. Furthermore, the heart size, heart weight/body weight ratios, cardiomyocyte size and apoptosis, interstitial collagen, hypertrophic markers including ANP and BNP expression were also significantly increased, which were effectively suppressed by IMD supplementation. In addition, IMD induced capillary angiogenesis and improved functions in hypertrophic hearts. We further observed that IMD induced strong autophagy in hypertrophic hearts and cultured cells, which was paralleling with the decrease in cardiomyocyte size and apoptosis. Furthermore, an autophagy inhibitor, 3-MA, was used to block the IMD-augmented autophagy level, and then the protection of IMD on cardiomyocyte hypertrophy and apoptosis was almost abrogated. We also observed that IMD supplementation stirred intracellular cAMP production, and augmented the ERK1/2 phosphorylation induced by Ang II/ISO exposure in H9c2 cells. In addition, we inhibited PI3K, PKA and MAPK/ERK1/2 signaling pathways by using wortamannin, H89 and PD98059, respectively, in H9c2 cells co-incubating with both IMD and Ang II or ISO, and observed that these inhibitors effectively reduced IMD-augmented autophagy level, but only H89 and PD98059 pre-incubation abrogated the anti-apoptotic action of IMD. These results indicate that the endogenous IMD and its receptor complexes are induced in hypertrophic cardiomyocytes and proposed to play an important role in the pathogenesis of cardiac hypertrophy, and the autophagy stirred by IMD supplementation is involved in its protection against cardiomyocyte hypertrophy and apoptosis through the activation of both cAMP/PKA and MAPK/ERK1/2 pathways.

反馈

验证码:
看不清楚,换一个
确定
取消

成果认领

标题:
用户 作者 通讯作者
请选择
请选择
确定
取消

提示

该栏目需要登录且有访问权限才可以访问

如果您有访问权限,请直接 登录访问

如果您没有访问权限,请联系管理员申请开通

管理员联系邮箱:yun@hnwdkj.com