title: Regulation of A-Kinase-Anchoring Protein 12 by Heat Shock Protein A12B to Prevent Ventricular Dysfunction Following Acute Myocardial Infarction in Diabetic Rats.
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.
authors.affiliation: Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut School of Medicine, Farmington Avenue, Farmington, CT, USA.
authors.forename: Vaithinathan
authors.initials: V
authors.lastname: Selvaraju
authors.affiliation: Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut School of Medicine, Farmington Avenue, Farmington, CT, USA.
authors.forename: Sumanth C
authors.initials: SC
authors.lastname: Suresh
authors.affiliation: Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut School of Medicine, Farmington Avenue, Farmington, CT, USA.
authors.forename: Mahesh
authors.initials: M
authors.lastname: Thirunavukkarasu
authors.affiliation: Centre for Bioinformatics, Pondicherry University, Pondicherry, India.
authors.forename: Jayakanthan
authors.initials: J
authors.lastname: Mannu
authors.affiliation: ESSEN BioScience, Ann Arbor, MI, USA.
authors.forename: Jocelyn L C
authors.initials: JLC
authors.lastname: Foye
authors.affiliation: Centre for Bioinformatics, Pondicherry University, Pondicherry, India.|KIIT University, Bhubaneshwar, India.
authors.forename: Premendu P
authors.initials: PP
authors.lastname: Mathur
authors.affiliation: Department of Surgery, Saint Mary's Hospital, Waterbury, CT, USA.
authors.forename: J Alexander
authors.initials: JA
authors.lastname: Palesty
authors.affiliation: Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut School of Medicine, Farmington Avenue, Farmington, CT, USA.
authors.forename: Juan A
authors.initials: JA
authors.lastname: Sanchez
authors.affiliation: Department of Surgery, University of Connecticut School of Medicine, Farmington Avenue, Farmington, CT, USA.
authors.forename: David W
authors.initials: DW
authors.lastname: McFadden
authors.affiliation: Molecular Cardiology and Angiogenesis Laboratory, Department of Surgery, University of Connecticut School of Medicine, Farmington Avenue, Farmington, CT, USA. nmaulik@uchc.edu.
authors.forename: Nilanjana
authors.initials: N
authors.lastname: Maulik
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D005355:Fibrosis; D005786:Gene Expression Regulation; D015316:Genetic Therapy / Q000379:methods*; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism*; D006801:Humans; D062105:Molecular Docking Simulation; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000628:therapy*; D018919:Neovascularization, Physiologic; D011485:Protein Binding; D034622:RNA Interference; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D018487:Ventricular Dysfunction, Left / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D016277:Ventricular Function, Left
chemical_list: D054758:A Kinase Anchor Proteins; C491162:AKAP12 protein, human; C102361:Akap12 protein, rat; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D018840:HSP70 Heat-Shock Proteins; C472131:HSPA12B protein, human; C552943:HSPA12B protein, rat; C493796:TXNIP protein, rat; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat
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