title: 1,25(OH)2D3improves cardiac dysfunction, hypertrophy, and fibrosis through PARP1/SIRT1/mTOR-related mechanisms in type 1 diabetes.
abstract: Diabetic cardiomyopathy is one of the most important cardiac complications associated with diabetes. However, the mechanisms underlying diabetic cardiomyopathy remain unclear. The PARP1, SIRT1, and mTOR pathways have been implicated in cardiac diseases, and they are also associated with diabetes. 1,25(OH)2D3was recently recognized as a potential PARP1inhibitor in a macrophage cell line. The aim of our study was to investigate whether 1,25(OH)2D3can improve diabetic cardiomyopathy through a vitamin D receptor (VDR)-dependent mechanism associated with the PARP1/SIRT1/mTOR pathway.
  
  
  
  1,25(OH)2D3-treated diabetic rats displayed improved left ventricular wall thickness and end-diastolic/systolic diameter, end-diastolic/systolic volume, left ventricular ejection fraction, fractional shortening, atrial natriuretic peptide, and brain natriuretic peptide gene expression, and interstitial fibrosis compared with untreated diabetic rats, while silencing the VDR gene in DM rats blocked the above results. 1,25(OH)2D3treatment also decreased PARP1 and increased SIRT1 expression levels and repressed the phosphorylation of mTOR. Treating neonatal cardiomyocytes with 1,25(OH)2D3and a PARP1 inhibitor decreased PARP1 and increased SIRT1 protein expression.
  
  
  
  The present study demonstrates that 1,25(OH)2D3treatment has the potential to improve diabetic cardiomyopathy in rats and suggests that VD-VDR signaling induces this protective effect against diabetic cardiomyopathy might partly through the PARP1/SIRT1/mTOR pathway.
authors: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors: Hua
authors: H
authors: Qu
authors: Department of Neurology, Chongqing Emergency Medical Center (The Fourth People's Hospital of Chongqing), Chongqing, P. R. China.
authors: Ke
authors: K
authors: Lin
authors: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors: Hang
authors: H
authors: Wang
authors: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors: Huili
authors: H
authors: Wei
authors: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors: Baolan
authors: B
authors: Ji
authors: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors: Zengsong
authors: Z
authors: Yang
authors: Laboratory of Lipid and Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors: Chuan
authors: C
authors: Peng
authors: Laboratory of Lipid and Glucose Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors: Xiaoqiu
authors: X
authors: Xiao
authors: Department of Endocrinology, the First Affiliated Hospital of Chongqing Medical University, Chongqing, P. R. China.
authors: Huacong
authors: H
authors: Deng
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D058065:Diabetic Cardiomyopathies / Q000188:drug therapy*; D005355:Fibrosis; D006321:Heart / Q000503:physiopathology*; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D006984:Hypertrophy; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D000071137:Poly (ADP-Ribose) Polymerase-1 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D018167:Receptors, Calcitriol; C499322:Parp1 protein, rat; D000071137:Poly (ADP-Ribose) Polymerase-1; C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D002117:Calcitriol
keywords: Cardiac dysfunction; Diabetes mellitus; Fibrosis; Hypertrophy; Vitamin D