title: Impaired sonic hedgehog pathway contributes to cardiac dysfunction in type 1 diabetic mice with myocardial infarction.
abstract: OBJECTIVE
  The incidence and mortality of myocardial infarction (MI) in diabetic patients are higher than in non-diabetic patients; however, the mechanisms by which diabetes results in cardiac dysfunction are poorly understood. The present study tested the hypothesis that an impaired sonic hedgehog (Shh) pathway contributes to cardiac dysfunction in type 1 diabetic mice with MI.
  
  
  RESULTS
  Adult male C57/B6 mice and streptozotocin-induced type 1 diabetic mice were used. Myocardial proteins of Shh, Patched-1 (Ptc1), and glioma-associated oncogene-1 (Gli1) were significantly decreased in type 1 diabetic mice at 10 weeks, and this was accompanied by cardiac dysfunction. Although myocardial proteins of Shh, Ptc1, and Gli1 were significantly increased 7 days after MI compared with the sham group in control mice, these proteins were markedly decreased in streptozotocin-induced diabetic mice. Treatment with Shh pathway agonist for 21 days significantly increased Ptc1 and Gli1 proteins, enhanced capillary density, reduced the percentage myocardial infarct, and then improved cardiac function in diabetic mice with MI compared with those with no drug treatment. This treatment had no effects in control mice with MI. Conversely, treatment with Shh pathway antagonist for 21 days significantly decreased Ptc1 and Gli1 proteins, reduced capillary density, enlarged the percentage myocardial infarct, and then exacerbated cardiac dysfunction in control mice with MI compared with those with no drug treatment.
  
  
  CONCLUSIONS
  These findings indicate that in type 1 diabetic mice the myocardial Shh pathway is impaired and that the impaired Shh pathway contributes to cardiac dysfunction. Strategies that are aimed at augmenting the Shh pathway may offer useful means for improving diabetic cardiac dysfunction.
authors: Department of Pharmacology,  Guangzhou Medical University, Guangzhou 510182,  PR China.
authors: Qing
authors: Q
authors: Xiao
authors: Ning
authors: N
authors: Hou
authors: Yan-Ping
authors: YP
authors: Wang
authors: Li-Shan
authors: LS
authors: He
authors: Yan-Hua
authors: YH
authors: He
authors: Gui-Ping
authors: GP
authors: Zhang
authors: Quan
authors: Q
authors: Yi
authors: Shi-Ming
authors: SM
authors: Liu
authors: Min-Sheng
authors: MS
authors: Chen
authors: Jian-Dong
authors: JD
authors: Luo
mesh_terms: D000818:Animals; D002196:Capillaries / Q000378:metabolism / Q000503:physiopathology; D002316:Cardiotonic Agents / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D053823:Hedgehog Proteins / Q000187:drug effects / Q000378:metabolism*; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D018919:Neovascularization, Physiologic; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010879:Piperazines / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013318:Stroke Volume; D013997:Time Factors; D015854:Up-Regulation; D016277:Ventricular Function, Left; D000071676:Zinc Finger Protein GLI1
chemical_list: D002316:Cardiotonic Agents; C498520:Gli1 protein, mouse; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D000072079:Patched Receptors; D000072081:Patched-1 Receptor; D010879:Piperazines; C000606240:Ptch1 protein, mouse; D011720:Pyrazoles; D011956:Receptors, Cell Surface; C468919:SANT-1 compound; C465570:Shh protein, mouse; D000071676:Zinc Finger Protein GLI1