title: AdipoR1/APPL1 potentiates the protective effects of globular adiponectin on angiotensin II-induced cardiac hypertrophy and fibrosis in neonatal rat atrial myocytes and fibroblasts.
abstract: Atrial hypertrophy and fibrosis are essential pathological features of atrial fibrillation. Recently, adiponectin has become a protein of interest due to its beneficial effects on cardiovascular diseases. However, the molecular mechanism of atrial structural remodeling and signaling pathways evoked by adiponectin remain unclear. In the present study, we investigated the cardioprotective effect of globular adiponectin (gAcrp) on angiotensin II-induced atrial hypertrophy and fibrosis in neonatal Sprague-Dawley rat. To further investigate the molecular mechanisms underlying the preventive effect of gAcrp, transfection of cells with siRNA was used to suppress the mRNA expression of adiponectin receptor 1 (AdipoR1) and its downstream adaptor protein APPL1. Non-silencing-Cy-3 labelled siRNA was used to determine transfection efficiency using fluorescence microscopy. The expression of atrial natriuretic peptide and procollagen type1 α-1, hypertrophy marker and fibrosis one, respectively, was detected by real-time PCR. Furthermore, the expression of adenosine monophosphate-activated protein kinase (AMPK), phosphatidylinositol 3-kinase (PI3K) and Akt was detected by western blotting. In addition, nuclear p65 translocation activity was analyzed by EMSA supershift assay. Our results showed that AdipoR1 and the adaptor protein APPL1 mediated the protective effects of gAcrp. In addition, the function of adiponectin and phosphorylation of AMPK were prominently diminished by inhibition of PI3K. Furthermore, nuclear factor-κB (NF-κB) transcription was diminished by the specific inhibition of AMPK. Taken together, AMPK pivotally interacts with NF-κB and PI3K, mediating the cardioprotective effect of adiponectin, and may serve as a therapeutic target for preventing atrial hypertrophy and fibrosis. Our present study suggests that gAcrp could ameliorate AngII-induced cardiac hypertrophy and fibrosis in rat atrial cells, which is mediated by the activation of AMPK signaling pathways. APPL1 and AdipoR1 are the key factors involved in the downstream of gAcrp approach.
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, P.R. China.
authors.forename: Tengwei
authors.initials: T
authors.lastname: Cao
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, P.R. China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Gao
authors.affiliation: Division of Cardiology, Jiangyin Hospital Affiliated to Southeast University, Jiangyin, P.R. China.
authors.forename: Lingyun
authors.initials: L
authors.lastname: Gu
authors.affiliation: Division of Cardiology, Department of Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Minglong
authors.initials: M
authors.lastname: Chen
authors.affiliation: Division of Cardiology, Department of Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Bing
authors.initials: B
authors.lastname: Yang
authors.affiliation: Division of Cardiology, Department of Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Kejiang
authors.initials: K
authors.lastname: Cao
authors.affiliation: College of Biotechnology and Pharmaceutical Engineering, Nanjing Tech University, Nanjing, P.R. China; State Key Laboratory of Materials-Oriented Chemical Engineering, Nanjing, P.R. China.
authors.forename: He
authors.initials: H
authors.lastname: Huang
authors.affiliation: Division of Cardiology, Department of Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, P.R. China.
authors.forename: Mingfang
authors.initials: M
authors.lastname: Li
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D052242:Adiponectin / Q000378:metabolism*; D000804:Angiotensin II / Q000009:adverse effects* / Q000494:pharmacology; D000818:Animals; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D004719:Endomyocardial Fibrosis / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D006325:Heart Atria / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D054419:Receptors, Adiponectin / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000009:adverse effects* / Q000494:pharmacology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D052242:Adiponectin; C515694:Appl1 protein, rat; D016328:NF-kappa B; D009419:Nerve Tissue Proteins; D054419:Receptors, Adiponectin; D014662:Vasoconstrictor Agents; C504339:adiponectin receptor 1, rat; D000804:Angiotensin II; D019869:Phosphatidylinositol 3-Kinases; D055372:AMP-Activated Protein Kinases
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