Dalton Cardiovascular Research Center

University of Missouri

Chandrasekar Bysani, D.V.M., Ph.D.

Margaret Proctor Mulligan Endowed Professor
Office Location: Harry S. Truman Memorial Veterans Hospital
Office Phone: 573-814-6000
chandrasekarb@health.missouri.edu

Research Interests

Cardiovascular

Research Description

We focus on understanding the patho-physiology of cardiovascular diseases, specifically on investigating the role of pro-inflammatory cytokines and chemokines in cardiovascular disease progression, including ischemic heart disease, pressure-overload hypertrophy, and heart failure. Recently, we identified TRAF3IP2 as a nodal point through which various signal transduction pathways can converge. TRAF3IP2 activates two critical pathways that lead to the induction of NF-kB, AP-1 and C/EBPb, and the induction of inflammatory cytokines with negative inotropic effects. TRAF3IP2 gene deletion markedly reduces myocardial injury and vastly improves post-ischemic myocardial recovery and function.

We have also found that expression of RECK, an MMP inhibitor, is significantly suppressed in the injured heart, resulting in progressive and adverse myocardial remodeling. To understand the role of RECK further, we have generated cardiac-specific knockout and overexpressing transgenic mice.

Our current studies are focused on identifying pharmacological inhibitors of TRAF3IP2 and inducers of RECK, and determine their therapeutic potential in adverse myocardial remodeling and progression to heart failure.

Professional Background

Oct 2009-to date: Professor with tenure, Heart and Vascular Institute, Tulane University School of Medicine, New Orleans, LA

Oct 2009- to date: Research Health Scientist, Southeast Louisiana Veterans Health Care System, New Orleans, LA

March 2009-to date: Research Administrator, Southeast Louisiana Veterans Health Care System, New Orleans, LA

July 1, 2011- to date: Member, R & D Committee at Southeast Louisiana Veterans Health Care System – 629

September 2011 to date: Chair, IACUC at Southeast Louisiana Veterans Health Care System – 629

Selected Publications

1. Murray DR, Mummidi S, Valente AJ, Yoshida T, Somanna N, Delafontaine P, Dinarello CA, and Chandrasekar B. b2 adrenergic activation induces the expression of IL-18 binding protein, a potent inhibitor of isoproterenol induced cardiomyocyte hypertrophy in vitro and myocardial hypertrophy in vivo. J Mol Cell Cardiol. 2012 Jan;52(1):206-18.
2. Valente AJ, Yoshida T, Gardner J, Somanna N, Delafontaine P, Chandrasekar B. Interleukin-17A stimulates cardiac fibroblast proliferation and migration via negative regulation of the dual-specificity phosphatase MKP-1. Cellular Signalling 2012 Feb;24(2):560-8.
3. Valente AJ, Clark RA, Siddesha JM, Siebenlist U, Chandrasekar B. CIKS (Act1 or TRAF3IP2) mediates Angiotensin-II-induced Interleukin-18 expression, and Nox2-dependent cardiomyocyte hypertrophy. J Mol Cell Cardiol. 2012 Jul;53(1):113-24.
4. Valente AJ, Yoshida T, Murthy SN, Sakamuri SS, Katsuyama M, Clark RA, Delafontaine P, Chandrasekar B. Angiotensin-II enhances AT1-Nox1 binding, and stimulates arterial smooth muscle cell migration and proliferation through AT1, Nox1, and interleukin-18. Am J Physiol Heart Circ Physiol. 2012 Aug 1;303(3):H282-96.
5. Venkatesan B, Valente AJ, Das NA, Carpenter AJ, Yoshida T, Delafontaine J-L, Siebenlist U, Chandrasekar B. CIKS (Act1 or TRAF3IP2) mediates high glucose-induced endothelial dysfunction. Cell Signal 2013; 25: 359–371.
6. Valente AJ, Yoshida T, Clark RA, Delafontaine P, Siebenlist U, Chandrasekar B. Advanced oxidation protein products induce cardiomyocyte death via Nox2/Rac1/superoxide-dependent TRAF3IP2 /JNK signaling. Free Radic Biol Med. 2013; 60: 125-135.
7. Valente AJ, Yoshida T, Izadpanah R, Delafontaine J-L, Siebenlist U, Chandrasekar B. Interleukin-18 enhances IL-18R/Nox1 binding, and mediates TRAF3IP2-dependent smooth muscle cell migration. Inhibition by simvastatin. Cell Signal 2013 (in press).
8. Valente AJ, Sakamuri SS, Siddesha JM, Yoshida T, Gardner JD, Prabhu R, Siebenlist U, Chandrasekar B. TRAF3IP2 mediates interleukin-18-induced cardiac fibroblast migration and differentiation. Cell Signal. 2013 Nov;25(11):2176-84.
9. Siddesha JM, Valente AJ, Sakamuri SS, Yoshida T, Gardner JD, Somanna N, Takahashi C, Noda M, Chandrasekar B. Angiotensin II stimulates cardiac fibroblast migration via the differential regulation of matrixins and RECK. J Mol Cell Cardiol. 2013 Dec;65:9-18.
10. Siddesha JM, Valente AJ, Sakamuri SS, Gardner JD, Delafontaine P, Noda M, Chandrasekar B. Acetylsalicylic acid inhibits IL-18-induced cardiac fibroblast migration through the induction of RECK. J Cell Physiol. 2014 Jul;229(7):845-55.
11. Siddesha JM, Valente AJ, Yoshida T, Sakamuri SS, Delafontaine P, Iba H, Noda M, Chandrasekar B. Docosahexaenoic acid reverses angiotensin II-induced RECK suppression and cardiac fibroblast migration. Cell Signal. 2014 May;26(5):933-41.
12. Valente AJ, Irimpen AM, Siebenlist U, Chandrasekar B. OxLDL induces endothelial dysfunction and death via TRAF3IP2: inhibition by HDL3 and AMPK activators. Free Radic Biol Med. 2014 May;70:117-28.
13. Yoshida T, Friehs I, Mummidi S, del Nido PJ, Addulnour-Nakhoul S, Delafontaine P, Valente AJ, Chandrasekar B. Pressure overload induces IL-18 and IL-18R expression, but markedly suppresses IL-18BP expression in a rabbit model. IL-18 potentiates TNF-α-induced cardiomyocyte death. J Mol Cell Cardiol. 2014 Oct;75:141-51.
14. Somanna NK, Yariswamy M, Garagliano JM, Siebenlist U, Mummidi S, Valente AJ, Chandrasekar B. Aldosterone-induced cardiomyocyte growth, and fibroblast migration and proliferation are mediated by TRAF3IP2. Cell Signal. 2015 Oct;27(10):1928-38.
15. Somanna NK, Valente AJ, Krenz M, Fay WP, Delafontaine P, Chandrasekar B. The Nox1/4 dual inhibitor GKT137831 or Nox4 knockdown inhibits Angiotensin-II-induced adult mouse cardiac fibroblast proliferation and migration. AT1 physically associates with Nox4. J Cell Physiol. 2015 (in press; PMID: 26445208).