title: Renal Denervation Findings on Cardiac and Renal Fibrosis in Rats with Isoproterenol Induced Cardiomyopathy.
abstract: Cardio-renal fibrosis plays key roles in heart failure and chronic kidney disease. We sought to determine the effects of renal denervation (RDN) on cardiac and renal fibrosis in rats with isoproterenol induced cardiomyopathy. Sixty male Sprague Dawley rats were randomly assigned to Control (n = 10) and isoproterenol (ISO)-induced cardiomyopathy group (n = 50). At week 5, 31 survival ISO-induced cardiomyopathy rats were randomized to RDN (n = 15) and Sham group (n = 16). Compared with Control group, ejection fraction was decreased, diastolic interventricular septal thickness and left atrial dimension were increased in ISO-induced cardiomyopathy group at 5 week. After 10 weeks, cardio-renal pathophysiologic results demonstrated that the collagen volume fraction of left atrio-ventricular and kidney tissues reduced significantly in RDN group compared with Sham group. Moreover the pro-fibrosis factors (TGF-β1, MMP2 and Collagen I), inflammatory cytokines (CRP and TNF-α), and collagen synthesis biomarkers (PICP, PINP and PIIINP) concentration significantly decreased in RDN group. Compared with Sham group, RDN group showed that release of noradrenaline and aldosterone were reduced, angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/angiotensin II type-1 receptor (AT1R) axis was downregulated. Meanwhile, angiotensin-converting enzyme 2 (ACE2)/angiotensin-1-7 (Ang-(1-7))/mas receptor (Mas-R) axis was upregulated. RDN inhibits cardio-renal fibrogenesis through multiple pathways, including reducing SNS over-activity, rebalancing RAAS axis.
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University.
authors.forename: Qian
authors.initials: Q
authors.lastname: Liu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University.
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University.
authors.forename: Kai
authors.initials: K
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University.
authors.forename: Shengchan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University.
authors.forename: Dasheng
authors.initials: D
authors.lastname: Lu
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University.
authors.forename: Zhenzhen
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University.
authors.forename: Jie
authors.initials: J
authors.lastname: Geng
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University.
authors.forename: Ping
authors.initials: P
authors.lastname: Fang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University.
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University.
authors.forename: Qijun
authors.initials: Q
authors.lastname: Shan
mesh_terms: D000804:Angiotensin II / Q000097:blood; D000818:Animals; D015415:Biomarkers / Q000097:blood; D009202:Cardiomyopathies / Q000097:blood / Q000139:chemically induced* / Q000150:complications* / Q000000981:diagnostic imaging; D016207:Cytokines / Q000097:blood; D003714:Denervation; D005355:Fibrosis; D006325:Heart Atria / Q000473:pathology; D006352:Heart Ventricles / Q000473:pathology; D018836:Inflammation Mediators / Q000378:metabolism; D007545:Isoproterenol; D007668:Kidney / Q000294:innervation* / Q000473:pathology*; D007674:Kidney Diseases / Q000097:blood / Q000150:complications* / Q000473:pathology*; D008297:Male; D009206:Myocardium / Q000473:pathology*; D020097:Natriuretic Peptide, Brain; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D010446:Peptide Fragments; D011347:Procollagen; C041876:procollagen Type III-N-terminal peptide; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D007545:Isoproterenol