title: Blockade of receptor for advanced glycation end products protects against systolic overload-induced heart failure after transverse aortic constriction in mice.
abstract: Heart failure is the consequence of sustained, abnormal neurohormonal and mechanical stress and remains a leading cause of death worldwide. The aim of this work was to identify whether blockade of receptor for advanced glycation end products (RAGE) protected against systolic overload-induced heart failure and investigate the possible underlying mechanism. It was found that RAGE mRNA and protein expression was up-regulated in cardiac tissues from mice subjected to pressure overload by transverse aortic constriction (TAC). Importantly, inhibition of RAGE by treatment with soluble RAGE (sRAGE) or FPS-ZM1 (a high-affinity RAGE-specific inhibitor) for 8 weeks attenuated cardiac remodeling (including cardiac hypertrophy and fibrosis), and dysfunction in mice exposed to TAC. Furthermore, treatment of TAC mice with sRAGE or FPS-ZM1 enhanced phosphorylation of AMPK and reduced phosphorylation of mTOR and protein expression of NFκB p65 in cardiac tissues. In addition, treatment of TAC mice with sRAGE or FPS-ZM1 abated oxidative stress, attenuated endoplasmic reticulum stress, and suppressed inflammation in cardiac tissues. These data demonstrated the benefits of blocking RAGE on the progression of systolic overload-induced heart failure in mice, which was possibly through modulating AMPK/mTOR and NFκB pathways.
authors.affiliation: Department of Cardiology, Jinling Hospital, Nanjing University, Zhongshan East Road 305, Nanjing 210002, China; Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Manli
authors.initials: M
authors.lastname: Yu
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yunhua
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Cardiovasology, Changhai Hospital, Second Military Medical University, Shanghai, China. Electronic address: xianxianz2010@163.com.
authors.forename: Xianxian
authors.initials: X
authors.lastname: Zhao
mesh_terms: D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology*; D001549:Benzamides / Q000494:pharmacology / Q000627:therapeutic use; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D005355:Fibrosis; D017127:Glycation End Products, Advanced / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D006333:Heart Failure / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D006984:Hypertrophy / Q000150:complications; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D011312:Pressure / Q000009:adverse effects*; D000067759:Receptor for Advanced Glycation End Products / Q000037:antagonists & inhibitors*; D015398:Signal Transduction / Q000187:drug effects; D012995:Solubility; D013599:Systole / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: C000593873:Ager protein, mouse; D001549:Benzamides; C572629:FPS-ZM1; D017127:Glycation End Products, Advanced; D016328:NF-kappa B; D000067759:Receptor for Advanced Glycation End Products; D058570:TOR Serine-Threonine Kinases
keywords: AMPK/mTOR; Heart failure; NFκB; Receptor for advanced glycation end products; Transverse aortic constriction