title: HSPA12B attenuates cardiac dysfunction and remodelling after myocardial infarction through an eNOS-dependent mechanism.
abstract: OBJECTIVE
  HSPA12B is a newly discovered and endothelial-cell-specifically expressed heat shock protein. We have reported recently that overexpression of HSPA12B increased endothelial nitric oxide synthase (eNOS) expression in mouse cardiac tissues during endotoxemia. Endothelial NOS has been shown to protect heart from ischaemic injury. We hypothesized that overexpression of HSPA12B will attenuate cardiac dysfunction and remodelling after myocardial infarction (MI) through an eNOS-dependant mechanism.
  
  
  RESULTS
  MI was induced by permanent ligation of the left anterior descending coronary artery in the transgenic mice (Tg) overexpressing hspa12b gene and its wild-type (WT) littermates. Echocardiographic analysis revealed that Tg mice exhibited improvements in cardiac dysfunction and remodelling at 1 and 4 weeks after MI. These improvements were accompanied by a significant decrease in cardiomyocyte apoptosis and increase in capillary and arteriolar densities. Significant up-regulation of eNOS, VEGF, Ang-1, and Bcl-2 was also observed in Tg hearts compared with WT hearts after MI. However, pharmacological inhibition of eNOS abolished the HSPA12B-induced decrease in cardiomyocyte apoptosis and increase in capillary formation after MI. Most importantly, inhibition of eNOS abrogated the protection of HSPA12B against cardiac dysfunction and remodelling after MI.
  
  
  CONCLUSIONS
  These data demonstrate for the first time that the overexpression of HSPA12B attenuates cardiac dysfunction and remodelling after MI. This action of HSPA12B was mediated, at least in part, by prevention of cardiomyocyte apoptosis and promotion of myocardial angiogenesis via an eNOS-dependent mechanism. HSPA12B could be a novel target for the management of patients with post-MI cardiac dysfunction and remodelling.
authors.affiliation: Department of Anesthesiology, First Affiliated Hospital with Nanjing Medical University, China.
authors.forename: Jingjin
authors.initials: J
authors.lastname: Li
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Li
authors.forename: Jian
authors.initials: J
authors.lastname: Xie
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.forename: Weina
authors.initials: W
authors.lastname: Zhu
authors.forename: Xiaojin
authors.initials: X
authors.lastname: Zhang
authors.forename: Surong
authors.initials: S
authors.lastname: Jiang
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Zhengnian
authors.initials: Z
authors.lastname: Ding
mesh_terms: D000818:Animals; D017209:Apoptosis; D005355:Fibrosis; D018840:HSP70 Heat-Shock Proteins / Q000502:physiology*; D006321:Heart / Q000503:physiopathology; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000473:pathology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D018919:Neovascularization, Physiologic; D052250:Nitric Oxide Synthase Type III / Q000502:physiology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D042461:Vascular Endothelial Growth Factor A / Q000032:analysis; D020257:Ventricular Remodeling
chemical_list: D018840:HSP70 Heat-Shock Proteins; C472131:HSPA12B protein, human; D019253:Proto-Oncogene Proteins c-bcl-2; D042461:Vascular Endothelial Growth Factor A; D052250:Nitric Oxide Synthase Type III; D019331:NG-Nitroarginine Methyl Ester
keywords: Cardiac dysfunction; Cardiac remodelling; Endothelial NOS (eNOS); Heat shock protein A12B (HSPA12B); Myocardial infarction