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

Vaithinathan Selvaraju, Sumanth C. Suresh, Mahesh Thirunavukkarasu, Jayakanthan Mannu, Jocelyn L.C. Foye, Premendu P. Mathur, J. Alexander Palesty, Juan Sanchez, David W. McFadden, Nilanjana Maulik

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)209-220
Number of pages12
JournalJournal of Cardiovascular Translational Research
Volume10
Issue number2
DOIs
StatePublished - Apr 1 2017
Externally publishedYes

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Ventricular Dysfunction
Thioredoxins
Protein Kinases
Myocardial Infarction
Staphylococcal Protein A
Streptozocin
Adenoviridae
Vascular Endothelial Growth Factor A
Proteins
Fibrosis
Down-Regulation
Western Blotting
Control Groups
Injections
S cerevisiae HSP12 protein

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
  • Vaithinathan Selvaraju and Sumanth C Suresh both contributed equally
  • VEGF

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Pharmaceutical Science
  • Cardiology and Cardiovascular Medicine
  • Genetics(clinical)

Cite this

Regulation of A-Kinase-Anchoring Protein 12 by Heat Shock Protein A12B to Prevent Ventricular Dysfunction Following Acute Myocardial Infarction in Diabetic Rats. / Selvaraju, Vaithinathan; Suresh, Sumanth C.; Thirunavukkarasu, Mahesh; Mannu, Jayakanthan; Foye, Jocelyn L.C.; Mathur, Premendu P.; Palesty, J. Alexander; Sanchez, Juan; McFadden, David W.; Maulik, Nilanjana.

In: Journal of Cardiovascular Translational Research, Vol. 10, No. 2, 01.04.2017, p. 209-220.

Research output: Contribution to journalArticle

Selvaraju, Vaithinathan ; Suresh, Sumanth C. ; Thirunavukkarasu, Mahesh ; Mannu, Jayakanthan ; Foye, Jocelyn L.C. ; Mathur, Premendu P. ; Palesty, J. Alexander ; Sanchez, Juan ; McFadden, David W. ; Maulik, Nilanjana. / Regulation of A-Kinase-Anchoring Protein 12 by Heat Shock Protein A12B to Prevent Ventricular Dysfunction Following Acute Myocardial Infarction in Diabetic Rats. In: Journal of Cardiovascular Translational Research. 2017 ; Vol. 10, No. 2. pp. 209-220.
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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.",
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