|Intermedin(1-53) protects against cardiac hypertrophy by inhibiting endoplasmic reticulum stress via activating AMP-activated protein kinase|
|Lu, Wei-Wei1,3; Zhao, Lei1,2; Zhang, Jin-Sheng1,3; Hou, Yue-Long3; Yu, Yan-Rong3; Jia, Mo-Zhi3; Tang, Chao-Shu1,2; Qi, Yong-Fen1,2,3|
|刊名||JOURNAL OF HYPERTENSION|
|WOS标题词||Science & Technology|
|类目[WOS]||Peripheral Vascular Disease|
|研究领域[WOS]||Cardiovascular System & Cardiology|
|关键词[WOS]||Spontaneously Hypertensive-rats ; Counter-regulatory Peptide ; Pressure-overload ; Therapeutic Target ; Oxidative Stress ; Cell-death ; Heart ; Expression ; Disease ; Injury|
Intermedin (IMD), a novel member of the calcitonin/calcitonin gene-related peptide family, is involved in maintaining circulatory homeostasis and is a protective factor of heart and vessel. Here, we investigated the effects of IMD on cardiac hypertrophy in vivo and in vitro and explored the mechanisms involved.
Methods and results:
IMD1-53 (100 ng/kg/h) was systemically administered to rats with cardiac hypertrophy induced by abdominal aortic constriction (AAC) by a mini-osmotic pump the next day after surgery continuously for 4 weeks. The AAC-treated rats before IMD infusion showed increased IMD content and expression of its receptors in the hearts. In-vivo administration of IMD1-53 greatly attenuated the cardiac hypertrophy as shown by heart weight to body weight ratio (HW/BW), haemodynamics, echocardiography, histological analyses and expression of hypertrophic markers atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) induced by AAC. IMD1-53 treatment significantly reduced the myocardial protein expression of endoplasmic reticulum stress (ERS) markers such as glucose-regulated protein 78 (GRP78), CCAAT/enhancer binding protein homologous protein (CHOP) and caspase-12, whereas the protein level of phosphorylated AMP-activated protein kinase (p-AMPK) was upregulated with IMD1-53 treatment, which was further confirmed in cultured cardiomyocytes. Concurrently, cardiomyocyte apoptosis in vivo and in vitro was ameliorated by IMD1-53 treatment. The inhibitory effects of IMD1-53 on ERS and apoptosis were eliminated on pretreatment with compound C, an AMPK inhibitor.
IMD1-53 could exert its cardioprotective effect on cardiac hypertrophy by inhibiting myocardial ERS and apoptosis, possibly via activation of AMPK signalling.
|项目编号||91339203 ; 81170082 ; 81270407|
|资助机构||National Natural Sciences Foundation of China ; Collaborative Innovation Center for Cardiovascular Disorders|
|作者单位||1.Peking Univ, Sch Basic Med Sci, Lab Cardiovasc Bioact Mol, Beijing 100871, Peoples R China|
2.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing, Peoples R China
3.Peking Univ, Hlth Sci Ctr, Sch Basic Med Sci, Dept Pathogen Biol, Beijing 100871, Peoples R China
|Lu, Wei-Wei,Zhao, Lei,Zhang, Jin-Sheng,et al. Intermedin(1-53) protects against cardiac hypertrophy by inhibiting endoplasmic reticulum stress via activating AMP-activated protein kinase[J]. JOURNAL OF HYPERTENSION,2015,33(8):1676-1687.|
|APA||Lu, Wei-Wei.,Zhao, Lei.,Zhang, Jin-Sheng.,Hou, Yue-Long.,Yu, Yan-Rong.,...&Qi, Yong-Fen.(2015).Intermedin(1-53) protects against cardiac hypertrophy by inhibiting endoplasmic reticulum stress via activating AMP-activated protein kinase.JOURNAL OF HYPERTENSION,33(8),1676-1687.|
|MLA||Lu, Wei-Wei,et al."Intermedin(1-53) protects against cardiac hypertrophy by inhibiting endoplasmic reticulum stress via activating AMP-activated protein kinase".JOURNAL OF HYPERTENSION 33.8(2015):1676-1687.|
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