Intermedin1–53 protects against cardiac hypertrophy by inhibiting endoplasmic reticulum stress via activating AMP-activated protein kinase. Issue 8 (August 2015)

• Record Type: Journal Article
• Authors: Lu, Wei-Wei; Zhao, Lei; Zhang, Jin-Sheng; Hou, Yue-Long; Yu, Yan-Rong; Jia, Mo-Zhi; Tang, Chao-Shu; Qi, Yong-Fen
• Is Part Of: Journal of hypertension. Volume 33:Issue 8(2015:Aug.)
• Publication Date: 2015-08
• Subjects: AMP-activated protein kinase -- calcitonin receptor-like receptor -- cardiac hypertrophy -- endoplasmic reticulum stress -- intermedin -- receptor activity-modifying proteins; Hypertension -- Periodicals; Hypertension -- Periodicals; 616.132005
• DOI: 10.1097/HJH.0000000000000597
• Languages: English
• ISSNs: 1473-5598

Abstract

Abstract : Objective: 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. Conclusion: IMD1–53 could exert its cardioprotective effect on cardiac hypertrophy by inhibiting myocardial ERS and apoptosis, possibly via activation of AMPK signalling. Abstract : Supplemental Digital Content is available in the text