title: The prevention of diabetic cardiomyopathy by non-mitogenic acidic fibroblast growth factor is probably mediated by the suppression of oxidative stress and damage.
abstract: BACKGROUND
  Emerging evidence showed the beneficial effect of acidic fibroblast growth factor (aFGF) on heart diseases. The present study investigated whether non-mitogenic aFGF (nm-aFGF) can prevent diabetic cardiomyopathy and the underlying mechanisms, if any.
  
  
  RESULTS
  Type 1 diabetes was induced in mice by multiple intraperitoneal injections of low-dose streptozotocin. Hyperglycemic and age-matched control mice were treated with or without nm-aFGF at 10 µg/kg daily for 1 and 6 months. Blood pressure and cardiac function were assessed. Cardiac H9c2 cell, human microvascular endothelial cells, and rat cardiomyocytes were exposed to high glucose (25 mM) for mimicking an in vitro diabetic condition for mechanistic studies. Oxidative stress, DNA damage, cardiac hypertrophy and fibrosis were assessed by real-time qPCR, immunofluorescent staining, Western blotting, and pathological examination. Nm-aFGF significantly prevented diabetes-induced hypertension and cardiac dysfunction at 6 months. Mechanistic studies demonstrated that nm-aFGF showed the similar preventive effect as the native aFGF on high glucose-induced oxidative stress (increase generation of reactive oxygen species) and damage (cellular DNA oxidation), cell hypertrophy, and fibrotic response (increased mRNA expression of fibronectin) in three kinds of cells. These in vitro findings were recaptured by examining the heart of the diabetic mice with and without nm-aFGF.
  
  
  CONCLUSIONS
  These results suggest that nm-aFGF can prevent diabetic cardiomyopathy, probably through attenuation of cardiac oxidative stress, hypertrophy, and fibrosis.
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Ruian Center of the Chinese-American Research Institute for Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Western University, London, Ontario, Canada ; Department of Pharmaceutical Engineering, Jilin Agriculture University, Changchun, Jilin, China.
authors.forename: Linbo
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Western University, London, Ontario, Canada.
authors.forename: Shali
authors.initials: S
authors.lastname: Chen
authors.affiliation: Department of Pathology, Western University, London, Ontario, Canada.
authors.forename: Biao
authors.initials: B
authors.lastname: Feng
authors.affiliation: Ruian Center of the Chinese-American Research Institute for Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Xuemian
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Cardiac Surgery, The First Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Bai
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Liang
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Departments of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, United States of America ; Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tan
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Ruian Center of the Chinese-American Research Institute for Diabetic Complications, The Third Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Minglong
authors.initials: M
authors.lastname: Shao
authors.affiliation: Departments of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Melissa
authors.initials: M
authors.lastname: Skibba
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; School of Pharmacy, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Litai
authors.initials: L
authors.lastname: Jin
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Department of Cardiac Surgery, The First Hospital of Jilin University, Changchun, Jilin, China.
authors.forename: Xiaokun
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Pathology, Western University, London, Ontario, Canada.
authors.forename: Subrata
authors.initials: S
authors.lastname: Chakrabarti
authors.affiliation: Chinese-American Research Institute for Diabetic Complications, Wenzhou Medical University, Wenzhou, Zhejiang, China ; Departments of Pharmacology and Toxicology, University of Louisville, Louisville, Kentucky, United States of America ; Kosair Children's Hospital Research Institute, Department of Pediatrics, University of Louisville, Louisville, Kentucky, United States of America.
authors.forename: Lu
authors.initials: L
authors.lastname: Cai
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D006332:Cardiomegaly / Q000150:complications / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D002460:Cell Line; D004249:DNA Damage; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology / Q000517:prevention & control*; D016220:Fibroblast Growth Factor 1 / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005355:Fibrosis; D005786:Gene Expression Regulation / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008934:Mitogens; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D001786:Blood Glucose; D008934:Mitogens; D012333:RNA, Messenger; D016220:Fibroblast Growth Factor 1