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 A. Sanchez; David W. McFadden; Nilanjana Maulik

doi:10.1007/s12265-017-9734-4

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 A. Sanchez, David W. McFadden, Nilanjana Maulik

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

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 language	English (US)
Pages (from-to)	209-220
Number of pages	12
Journal	Journal of cardiovascular translational research
Volume	10
Issue number	2
DOIs	https://doi.org/10.1007/s12265-017-9734-4
State	Published - Apr 1 2017
Externally published	Yes

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

ASJC Scopus subject areas

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

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10.1007/s12265-017-9734-4

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Selvaraju, V., Suresh, S. C., Thirunavukkarasu, M., Mannu, J., Foye, J. L. C., Mathur, P. P., Palesty, J. A., Sanchez, J. A., McFadden, D. W., & Maulik, N. (2017). Regulation of A-Kinase-Anchoring Protein 12 by Heat Shock Protein A12B to Prevent Ventricular Dysfunction Following Acute Myocardial Infarction in Diabetic Rats. Journal of cardiovascular translational research, 10(2), 209-220. https://doi.org/10.1007/s12265-017-9734-4

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 et al.
In: Journal of cardiovascular translational research, Vol. 10, No. 2, 01.04.2017, p. 209-220.

Research output: Contribution to journal › Article › peer-review

Selvaraju, V, Suresh, SC, Thirunavukkarasu, M, Mannu, J, Foye, JLC, Mathur, PP, Palesty, JA, Sanchez, JA, McFadden, DW & Maulik, N 2017, 'Regulation of A-Kinase-Anchoring Protein 12 by Heat Shock Protein A12B to Prevent Ventricular Dysfunction Following Acute Myocardial Infarction in Diabetic Rats', Journal of cardiovascular translational research, vol. 10, no. 2, pp. 209-220. https://doi.org/10.1007/s12265-017-9734-4

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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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AU - Selvaraju, Vaithinathan

AU - Suresh, Sumanth C.

AU - Thirunavukkarasu, Mahesh

AU - Mannu, Jayakanthan

AU - Foye, Jocelyn L.C.

AU - Mathur, Premendu P.

AU - Palesty, J. Alexander

AU - Sanchez, Juan A.

AU - McFadden, David W.

AU - Maulik, Nilanjana

PY - 2017/4/1

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N2 - 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.

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

Abstract

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ASJC Scopus subject areas

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