Suresh C. Tyagi, Ph.D.

University of Aligarh, India, 1980

Heart and Vascular Remodeling, Diabetes, Hypertension, Hyperhomocysteinemia

Our goal is to understand the mechanism of cardiovacular-renal remodeling in hypertension, diabetes, and heart failure. One of our principal aims is to understand the mechanism of dilation in the absence of endothelial nitric oxide. It is widely believed that nitric oxide is the primarily dilatory agent, direct or indirect. There are numerous circumstances when nitric oxide is diminished or tissue is without nitric oxide. In this situation the metalloproteinase is activated and dilates the tissue. The initial disruption of extracellular matrix is essential for cell survival. However, prolong disconnection between cell and matrix leads to cell death, necrosis or apoptosis. We employ two approaches:  1) create chronic heart failure by volume overload arteriovenous fistula; and 2) oxidative conditioning is created by homocysteine overload, using transgene and promoter dashing (on/off) genomic models. The specific cells responsible for pathogenesis are identified by employing laser dissecting microscope, differential display, and microarray analyses. The biochemical, molecular, and immunohistochemical techniques, along with ex vivo and in vivo physiological methods, are used to test our hypotheses.

Recent Publications:

  1. Tyagi N, Givvimani S, Qipshidze N, Kundu S, Kapoor S, Vacek JC, Tyagi SC. Hydrogen sulfide mitigates matrix metalloproteinase-9 activity and neurovascular permeability in hyperhomocysteinemic mice. Neurochem Int. Jan;56(2):301-7, 2010.
  2. Mishra PK, Tyagi N, Sen U, Givvimani S, Tyagi SC. H2S ameliorates oxidative and proteolytic stresses and protects the heart against adverse remodeling in chronic heart failure, Am J Physiol Heart Circ Physiol. Feb;298(2):H451-6, 2010.
  3. Tyagi N, Givvimani S, Mishra PK, Sen U, Tyagi SC. Cardiac specific deletion of N-methyl-D-aspartate receptor 1 ameliorates mtMMP- 9 mediated autophagy/mitophagy in hyperhomocysteinemia, J Recept Signal Transduct Res. Apr;30(2):78-87, 2010.
  4. Givvimani S,  Tyagi N, Sen U, Mishra PK, Quipshidze N, Munjal C, Abe QA, Tyagi SC. MMP-2/TIMP-2/TIMP-4 versus MMP-9/TIMP-3 in transition from compensatory hypertrophy and angiogenesis to de-compensatory heart failure,  Arch Physiol Biochem. May;116(2):63-72, 2010.
  5. Sen U, Munjal C, Qipshidze N, Abe O, Gargoum R,Tyagi SC. Hydrogen sulfide regulates homocysteine-mediated glomerulosclerosis. Am J Nephrol. 16;31(5):442-455, 2010.
  6. Basu P, Sen U, Tyagi N, Tyagi SC. Blood flow interplays with elastin/collagen and MMP/TIMP ratios to maintain healthy vascular structure and function in Spague-Dawley rats. Vasc Health Risk Manag. Apr 15;6:215-28, 2010.
  7. Holthouser K, Mandal A, Merchant ML, Schelling J, Delamere NA, Valdes RR, Tyagi SC, Lederer ED, Khundmiri SJ. Ouabain stimulates Na-K ATPase through sodium hydrogen exchanger-1 (NHE-1) dependent mechanism in human kidney proximal tubule cells. Am J Physiol Renal Physiol. Jul;299(1):F77-90, 2010.
  8. Mishra PK, Metreveli N, Tyagi SC. MMP-9 gene ablation and TIMP-4 mitigate PAR-1-mediated cardiomyocyte dysfunction: a plausible role of dicer and miRNA. Cell Biochem Biophys. Jul;57(2-3):67-76, 2010.
  9. Steed MM, Tyagi N, Sen U, Schuschke DA, Joshua IG, Tyagi SC. Functional Consequences of the Collagen/Elastin Switch in Vascular Remodeling in Hyperhomocysteinemic Wild Type, eNOS-/- and iNOS-/- Mice, Am J Physiol Lung Cell Mol Physiol. Sep;299(3):L301-11, 2010.
  10. Qipshidze N, Tyagi N, Sen U, Givvimani S, Metreveli N, Lominadze D, Tyagi SC. Folic Acid Mitigated Cardiac Dysfunction by Normalizing the Levels of Tissue Inhibitor of Metalloproteinase and homocysteine-metabolizing enzymes Post myocardial Infarction in Mice, Am J Physiol (Heart & Circ Physiol), 299(5):H1484-93, 2010.
  11. Mishra PK, Tyagi N, Sen U, Joshua IG, Tyagi SC. Synergism in hyperhomocysteinemia and diabetes: Role of PPAR and anti-oxidant, Cardiovascular diabetology, 9;9:49, 2010.
  12. Mishra PK, Givvimani S, Metreveli N, Tyagi SC. Beta 2-adrenergic receptors in diabetic cardiomyopathy of Insulin 2 mutant mice: a role of hyperhomocysteinemia, Biochem Biophys Res Commun. 15;401(2):175-81, 2010.
  13. Vacek TP, Glispie W, Tyagi N, Vacek JC, Tyagi SC. Hydrogen sulfide protects against vascular remodeling from endothelial damage, Amino Acids. 39(5):1161-9, 2010.
  14. Vacek TP, Metreveli N, Tyagi N, Vacek JC, Pagni S, Tyagi SC. Electrical stimulation of cardiomyocytes activates mitochondrial matrix metalloproteinase causing electrical remodeling, Biochem Biophys Res Commun. 21;404(3):762-6, 2011.
  15. Givvimani S, Sen U, Tyagi N, Munjal C, Tyagi SC. X-ray imaging of differential vascular density in MMP-9-/-, PAR-1-/+, hyperhomocysteinemic (CBS-/+) and diabetic (Ins2-/+) mice, Arch Physiol Biochem. 117(1):1-7, 2011.
  16. Sen U, Qipshidze N, Abe OA and Tyagi SC. Cystathionine -synthase and cystathionine -lyase double gene transfer ameliorated homocysteine-mediated mesangial inflammation through hydrogen sulfide generation. Am J Physiol Cell Physiol. 300(1):C155-63, 2011.
  17. Munjal C, Givvimani S, Qipshidze N, Tyagi N, Falcone JC, Tyagi SC. Mesenteric Vascular Remodeling in Hyperhomocysteinemia, Mol Cell Biochem. 348(1-2):99-108, 2011.
  18. Tyagi N, Vacek TP, Fleming JT, Vacek JC, Tyagi SC. Hyperhomocysteinemia Decreases Bone Blood Flow. Vascular Health and Risk Management, 7:31-35, 2011.
  19. Givvimani S Munjal C, Gargoum R, Tyagi N, Sen U, Vacek JC, Tyagi SC. Hydrogen sulfide mitigates transition from compensatory hypertrophy to heart failure through MMP-2 activation and angiogenesis. J Applied Physiol, Apr;110(4):1093-100, 2011.
  20. Mishra PK, Awe O, Metreveli N, Quipshidze N, Joshua IG, Tyagi SC. Exercise mitigates the homocysteine - beta2-adrenergic receptor interactions to ameliorate contractile dysfunction in diabetes, Intern J Physiol Pathophysiol & Pharmacol, 3(2):97-106, 2011.
  21. Rosenberger D, Gargoum R, Tyagi N, Metreveli N, Sen U, Maldonado C, Tyagi S. Homocysteine enriched diet leads to prolonged QT interval and reduced left ventricular performance in telemetric monitored mice. Nutr Metab Cardiovasc Dis. Jul;21(7):492-8, 2011.
  22. Givvimani S, Qipshidze N, Tyagi N, Mishra PK, Sen U, Tyagi SC. Synergism between arrhythmia and hyperhomocysteinemia in structural heart disease, Intern J of Physiol, Pathophysiol & Pharmacology, 3(2):107-119, 2011.
  23. Dahiya S, Givvimani S, Bhatnagar S, Qipshidze N, Tyagi SC, Kumar A. Osteopontin-Stimulated Expression of Matrix Metalloproteinase-9 Causes Cardiomyopathy in the mdx Model of Duchenne Muscular Dystrophy. J Immunol. 1;187(5):2723-31, 2011.
  24. Qipshidze N, Metreveli N, Lominadze D, Tyagi SC. Folic acid improves acetylcholine-induced vasoconstriction of coronary vessels isolated from hyperhomocysteinemic mice: an implication to coronary vasospasm. J Cell Physiol. 226(10):2712-20, 2011.
  25. Tyagi N, Kandel M, Munjal C, Qipshidze N, Vacek JC, Pushpakumar SB, Metreveli N, Tyagi SC. Homocysteine mediated decrease in bone blood flow and remodeling: role of folic acid. J Orthop Res. 29(10):1511-6, 2011.
  26. Tyagi N, Qipshidze N, Sen U, Rodriguez W, Ovechkin A, Tyagi SC. Cystathionine beta synthase gene dose dependent vascular remodeling in murine model of hyperhomocysteinemia. Int J Physiol Pathophysiol Pharmacol. 30;3(3):210-222, 2011.
  27. Basu P, Qipshidze N, Sen U, Givvimani S, Munjal C, Mishra PK, Tyagi SC. Chronic Hyperhomocysteinemia Causes Vascular Remodeling by Instigating Vein Phenotype in Artery. Archives of Physiology and Biochemistry, 117(5):270-82, 2011.
  28. Basu P, Qipshidze N, Sen U, Mishra PK, Tyagi SC. Remodeling of vein expresses arterial phenotype in chronic hyperhomocysteinemia. Int J Physiol Pathophysiol Pharmacol, 3(4):266-79, 2011.
  29. Qipshidze N, Tyagi N, Metreveli N, Lominadze D, Tyagi SC. Autophagic mechanism of right ventricular remodeling in murine model of pulmonary artery constriction, Am J Physiol Heart & Circ Physiol, 302(3):H688-96, 2012.
  30. Kundu S, Munjal C, Tyagi N, Sen U, Tyagi AC, Tyagi SC. Folic acid improves inner ear vascularization in hyperhomocysteinemic mice. Hear Res. 284(1-2):42-51, 2012.
  31. Tyagi N, Qipshidze N, Munjal C, Vacek JC, Metreveli N, Givvimani S, Tyagi SC. Tetrahydrocurcumin Ameliorates Homocysteinylated Cytochrome-c Mediated Autophagy in Hyperhomocysteinemia Mice after Cerebral Ischemia. J Mol Neurosci. 47(1):128-38, 2012.
  32. Muradashvili N,  Qipshidze N, Munjal C, Givvimani S. Benton R, Tyagi, SC, Lominadze D. Fibrinogen-induced increased pial venular permeability in mice. J Cerebral Blood Flow. 32(1):150-163, 2012.
  33. Qipshidze N, Metreveli N, Mishra P, Lominadze D, Tyagi SC. Hydrogen sulfide regulates cardiac function and structure during myocardial infarction in mice via improvement of angiogenesis, Intern J Biol Sci, 8(4):430-41, 2012.
  34. Mishra PK, Chavali V, Metreveli N, Tyagi SC. Ablation of MMP9 induces survival and differentiation of cardiac stem cells into cardiomyocytes in the heart of diabetics: a role of extracellular matrix. Can J Physiol Pharmacol. 90(3):353-60, 2012.
  35. Givvimani S, Munjal C, Sen U, Tyagi N, Metreveli N, Tyagi SC. Mitochondrial division/mitophagy inhibitor (Mdivi) ameliorates pressure overload induced heart failure. pLos, 7(3):e32388, 2012.
  36. Munjal C, Tyagi N, Lominadze D, Tyagi SC. Matrix Metalloproteinase-9 in Homocysteine-Induced Intestinal Microvascular Endothelial Paracellular and Transcellular Permeability, J Cell Biochem. 113(4):1159-69, 2012.
  37. Sen U, Sathnur PB, Kundu S, Givvimani S, Coley DM, Mishra PK, Qipshidze N, Tyagi N, Metreveli N, Tyagi SC. Increased endogenous H2S generation by CBS, CSE, and 3MST gene therapy improves ex vivo renovascular relaxation in hyperhomocysteinemia. Am J Physiol Cell Physiol. 2012 Jul;303(1):C41-51, 2012.
  38. Givvimani S, Munjal C, Narayanan N, Aqil F, Tyagi G, Metreveli N, Tyagi SC. Hyperhomocysteinemia decreases intestinal motility leading to constipation. Am J Physiol Gastrointest Liver Physiol. Aug;303(3):G281-90, 2012.
  39. Chavali V, Tyagi SC, Mishra PK. MicroRNA-133a regulates DNA methylation in diabetic cardiomyocytes. Biochem Biophys Res Commun. Aug 31;425(3):668-672, 2012.
  40. Klionsky DJ, et al Tyagi SC. et al, Guidelines for the use and interpretation of assays for monitoring autophagy. Autophagy. Apr;8(4):445-544, 2012.
  41. Passmore JC, Fleming JT, Tyagi SC, Falcone JC. Tyrosine kinase receptor alteration of renal vasoconstriction in rats is sex- and age-related. Can J Physiol Pharmacol. Oct;90(10):1372-9, 2012.
  42. Lominadze D, Tyagi N, Sen U, Ovechkin A, Tyagi SC. Homocysteine alters cerebral microvascular integrity and causes remodeling by antagonizing GABA-A receptor, Mol Cell Biochem, 371(1-2):89-96, 2012.
  43. Givvimani S, Kundu S, Narayanan N, Armaghan F, Qipshidze N, Pushpakumar S, Vacek TP, Tyagi SC. TIMP-2 mutant decreases MMP-2 activity and augments pressure overload induced LV dysfunction and heart failure. Arch Physiol Biochem. 119(2):65-74, 2013.
  44. Vacek TP, Kalani A, Voor MJ, Tyagi SC, Tyagi N. The role of homocysteine in bone remodeling. Clin Chem Lab Med. 1;51(3):579-90, 2013.
  45. Narayanan N, Tyagi N, Shah A, Pagni S, Tyagi SC. Hyperhomocysteinemia during aortic aneurysm, a plausible role of epigenetics. Int J Physiol Pathophysiol Pharmacol. 5(1):32-42, 2013.
  46. Chavali V, Tyagi SC, Mishra PK. Predictors and prevention of diabetic cardiomyopathy. Diabetes Metab Syndr Obes. Apr 11;6:151-60, 2013.
  47. Kalani A, Kamat PK, Tyagi SC, Tyagi N. Synergy of Homocysteine, MicroRNA, and Epigenetics: A Novel Therapeutic Approach for Stroke. Mol Neurobiol. 2013 Feb 22. [Epub ahead of print] PMID: 23430482
  48. Vacek TP, Qipshidze N, Tyagi SC. Hydrogen sulfide and sodium nitroprusside compete to activate/deactivate MMPs in bone tissue homogenates. Vasc Health Risk Manag. 2013;9:117-23. doi: 10.2147/VHRM.S39508. Epub 2013 Mar 19.
  49. Chavali V, Tyagi SC, Mishra PK. Differential expression of dicer, miRNAs and inflammatory markers in diabetic Ins2+/- Akita hearts. Cell Biochem. Biophys. In press, 2013.