Venkateswaran Subramanian, Ph.D.

Bio / Education: 
  • Bharathidasan University, India,  B.Sc., 1993, Chemistry
  • Annamalai University, India, M.Sc., 1995, Biochemistry
  • Annamalai University, India, M.Phil., 1997, Biochemistry
  • Annamalai University, India, Ph.D., 2003, Biochemistry
  • Postdoctoral Fellow, East Tennessee State University, Johnson City, TN, USA. Dr. Singh’s Laboratory
  • Postdoctoral Fellow, University of Kentucky Lexington, KY, USA. Dr. Daugherty’s Laboratory
Research Description: 

My research interests are to understand the molecular mechanisms of aortic vascular disease and obesity.  The primary focus of my research is to identify the functional role of calpain, a cysteine protease in the vascular diseases mainly, atherosclerosis and aortic aneurysms.  To delineate the functional contribution of calpain in vascular pathologies, we used an animal model of Angiotensin II (AngII) -induced aortic aneurysms and atherosclerosis developed by Dr. Daugherty and Dr. Cassis, at University of Kentucky.  Using this animal model, recently, we have demonstrated that pharmacological inhibition of calpains completely attenuate the development of AngII-induced aortic aneurysm in mice.  To further explore the molecular mechanisms by which calpain activation contributes to these vascular diseases, recently we have developed unique reagents including whole body or conditional cell-specific calpain deficient mice.  Using these novel reagents, in the coming years, we hope to identify the cell type and isoform specific, mechanistic role of calpains in these vascular diseases.

Grants: 

14SDG18740000 
01/2014 – 12/2017
American Heart Association
Role of macrophage-specific calpain-2 in hypercholesterolemia-induced atherosclerosis”
The focus of this project is to determine that calpain deficiency in macrophages will attenuate hypercholesterolemia-induced atherosclerosis by promoting macrophage RCT and suppressing NF-kB mediated inflammation.
Role: PI

5P20GM103527                                                                                                                                             08/2015 – 07/2017                                                                                                                                           National Institute of Health                                                                                                                        Center of Research in Obesity and Cardiovascular Disease. This is a center grant to create a research focus in the area of obesity and cardiovascular disease. The goal of this study is to determine the role of obesity in aortic aneurysm development.                                                    

Cassis (PI)                                                                                                                                                  Role: Junior Investigator

Selected Publications: 
  1. Subramanian V, Pari L, Suguna L, Chandrakasan G. Modulatory effect of Coccinia indica on aortic collagen in streptozotocin-induced diabetic rats. Clin Exp Pharmacol Physiol 2003; 30: 157-163. (PMID: 12603344)
  2. Subramanian V, Pari L. Effect of Coccinia indica leaf extract on plasma antioxidants in streptozotocin induced diabetes in rats. Phytother Res 2003; 17: 605-608. (PMID:12820255)
  3. Krishnamurthy P, Subramanian V, Singh M, Singh K. Deficiency of β1 integrins results in increased myocardial dysfunction after myocardial infarction. Heart 2006; 92: 1309- 1315. (PMCID: PMC1861145)
  4. Krishnamurthy P, Subramanian V, Singh M, Singh K.  β1 integrins modulate β-adrenergic receptor stimulated apoptosis and myocardial remodeling.  Hypertension 2007; 49: 865-872. (PMID: 17283249)
  5. Subramanian V, Krishnamurthy P, Singh K, Singh M. Lack of Osteopontin improves cardiac function in streptozotocin induced diabetic mice. Am J Physiol Heart Circ Physiol 2007; 293: H673-683. (PMID: 16980342)
  6. Krishnamurthy P, Peterson JT, Subramanian V, Singh M, Singh K. Inhibition of matrix metalloproteinases improves left ventricular function in mice lacking osteopontin after myocardial infarction. Mol Cell Biochem 2009; 322: 53-62. (PMCID: PMC2711544)
  7. Owens AP 3rd, Subramanian V, Moorleghen JJ, Guo Z, McNamara CA, Cassis LA, Daugherty A. Angiotensin II Induces a Region-Specific Hyperplasia of the Ascending Aorta Through Regulation of Inhibitor of Differentiation 3. Circ Res 2010; 106: 611-619. (PMCID: PMC2825288)
  8. Subramanian V, Golledge J, Ijaz T, Bruemmer D, Daugherty A. Pioglitazone-Induced Reductions in Atherosclerosis Occur via Smooth Muscle Cell–Specific Interaction With PPARγ. Circ Res 2010; 107: 953-958. (PMCID: PMC2963621)
  9. Rateri D, Moorleghen J, Balakrishnan A, Owens AP, Howatt DA, Subramanian V, Poduri A, Charnigo R, Cassis LA, Daugherty A.  Endothelial Cell-specific Deficiency of AngII Type 1a Receptors Attenuates AngII-induced Ascending Aortic Aneurysms in LDL Receptor -/- Mice. Circ Res 2011; 108: 574-581. (PMCID: PMC3076204)
  10. Foster CR, Singh M, Subramanian V, Singh K. Ataxia telangiectasis mutated kinase plays a protective role in β-adrenergic receptor stimulated cardiac yocyte apoptosis and myocardial remodelling. Mol Cell Biochem 2011; 353: 13-22. (PMCID: PMC3106113).
  11. Uchida HA, Poduri A, Subramanian V, Cassis LA, Daugherty A.  Urokinase-Type Plasminogen Activator Deficiency in Bone Marrow-Derived Cells Augments Rupture of Angiotensin II-Induced Abdominal Aortic Aneurysms. Arterioscler Thromb Vasc Biol 2011; 31: 2845-2852. (PMCID: PMC3220732)
  12. Wang S, Subramanian V, Lu H, Howatt DA, Moorleghen JJ, Charnigo R, Cassis LA, Daugherty A. Deficiency of receptor-associated protein attenuates angiotensin II-induced atherosclerosis in hypercholesterolemic mice without influencing abdominal aortic aneurysms. Atherosclerosis 2012; 220: 375-380. (PMCID: PMC3264806) 
  13. Subramanian V*, Golledge J, Heywood EB, Bruemmer D, Daugherty A. Regulation of Peroxisome Proliferator-Activated Receptor-γ by Angiotensin II Via Transforming Growth Factor-β1-Activated p38 Mitogen-Activated Protein Kinase in Aortic Smooth Muscle Cells. Arterioscler Thromb Vasc Biol 2012; 32: 397-405. (PMCID: 3262055)  *- Author for Correspondence.
  14. Subramanian V*, Uchida HA, Ijaz T, Moorleghen JJ, Howatt DA, Balakrishnan A. Calpain Inhibition Attenuates Angiotensin II-induced Abdominal Aortic Aneurysms and Atherosclerosis in LDL Receptor Deficient Mice.  J Cardiovasc Pharmacol 2012; 59: 66-76. (PMCID: PMC3248626) *- Author for Correspondence.
  15. Subramanian V*, Moorleghen JJ, Balakrishnan A, Howatt DA, Chishti AH, Uchida HA. Calpain-2 Compensation Promotes Angiotensin II-induced Ascending and Abdominal Aortic Aneurysms in Calpain-1 Deficient Mice. PLoS One 2013; 19: e72214. (PMCID: PMC3747148) *- Author for Correspondence.
  16. Howatt DA, Balakrishnan A, Moorleghen JJ, Muniappan L, Rateri DL, Uchida HA, Takano, J, Saido TC, Chishti AH, Baud L, Subramanian V*.  Leukocyte Calpain Deficiency Reduces Angiotensin II-induced Inflammation and Atherosclerosis but not Abdominal Aortic Aneurysms in Mice. Arterioscler Thromb Vasc Biol 2016, In Press. (PMID:26966280)  *- Author for Correspondence.
PubMed Publications: 

  • Howatt, D.A.;Balakrishnan, A.;Moorleghen, J.J.;Muniappan, L.;Rateri, D.L.;Uchida, H.A.;Takano, J.;Saido, T.C.;Chishti, A.H.;Baud, L.;Subramanian, V. "Leukocyte Calpain Deficiency Reduces Angiotensin II-Induced Inflammation and Atherosclerosis But Not Abdominal Aortic Aneurysms in Mice." Arteriosclerosis, thrombosis, and vascular biology 36, 5 (2016): 835-45. [PubMed Link] | [ Full text ]