Regulation of A-Kinase-Anchoring Protein 12 by Heat Shock Protein A12B to Prevent Ventricular Dysfunction Following Acute Myocardial Infarction in Diabetic Rats

J Cardiovasc Transl Res. 2017 Apr;10(2):209-220. doi: 10.1007/s12265-017-9734-4. Epub 2017 Mar 9.

Abstract

We examined the effects of overexpressing HSPA12B on angiogenesis and myocardial function by intramyocardial administration of adenovirus encoding HSPA12B (Ad. HSPA12B) in a streptozotocin-induced diabetic rat subjected to myocardial infarction. Rats were divided randomly into six groups: control sham (CS) + Ad.LacZ, control myocardial infarction (CMI) + Ad.LacZ, control MI + Ad.HSPA12B, diabetic sham (DS) + Ad.LacZ, diabetic MI + Ad.LacZ and diabetic MI + Ad.HSPA12B. Following MI or sham surgery, the respective groups received either Ad.LacZ or Ad.HSPA12B via intramyocardial injections. We observed increased capillary and arteriolar density along with reduced fibrosis and preserved heart functions in DMI-AdHSPA12B compared to DMI-AdLacZ group. Western blot analysis demonstrated enhanced HSPA12B, vascular endothelial growth factor (VEGF), thioredoxin-1 (Trx-1) expression along with decreased expression of thioredoxin interacting protein (TXNIP) and A kinase anchoring protein 12 (AKAP12) in the DMI-AdHSPA12B compared to DMI-AdLacZ group. Our findings reveal that HSPA12B overexpression interacts with AKAP12 and downregulate TXNIP in diabetic rats following acute MI.

Keywords: AKAP12; All authors take responsibility for all aspects of the reliability and freedom from bias of the data presented and their discussed interpretation.; Cardiovascular disease; Communicated by: Associate Editor Lorrie Kirshenbaum oversaw the review of this article.; Gene therapy; Myocardial infarction; VEGF; Vaithinathan Selvaraju and Sumanth C Suresh both contributed equally.

MeSH terms

  • A Kinase Anchor Proteins / genetics
  • A Kinase Anchor Proteins / metabolism*
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism*
  • Cell Movement
  • Cells, Cultured
  • Diabetes Mellitus, Experimental / genetics
  • Diabetes Mellitus, Experimental / metabolism
  • Diabetes Mellitus, Experimental / physiopathology
  • Diabetes Mellitus, Experimental / therapy*
  • Fibrosis
  • Gene Expression Regulation
  • Genetic Therapy / methods*
  • HSP70 Heat-Shock Proteins / genetics
  • HSP70 Heat-Shock Proteins / metabolism*
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Molecular Docking Simulation
  • Myocardial Infarction / genetics
  • Myocardial Infarction / metabolism
  • Myocardial Infarction / physiopathology
  • Myocardial Infarction / therapy*
  • Neovascularization, Physiologic
  • Protein Binding
  • RNA Interference
  • Rats, Sprague-Dawley
  • Signal Transduction
  • Time Factors
  • Transfection
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism
  • Ventricular Dysfunction, Left / genetics
  • Ventricular Dysfunction, Left / metabolism
  • Ventricular Dysfunction, Left / physiopathology
  • Ventricular Dysfunction, Left / prevention & control*
  • Ventricular Function, Left*

Substances

  • A Kinase Anchor Proteins
  • AKAP12 protein, human
  • Akap12 protein, rat
  • Carrier Proteins
  • Cell Cycle Proteins
  • HSP70 Heat-Shock Proteins
  • HSPA12B protein, human
  • HSPA12B protein, rat
  • TXNIP protein, rat
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, rat