Utpal Sen, Ph.D., F.A.H.A.

Utpal Sen, Ph.D., F.A.H.A.

Associate Professor
University of Kalyani, India, 2001

Renovascular remodeling in hypertension and diabetes: physiological roles of hydrogen sulfide

The goal of our laboratory is to delineate the mechanisms of kidney remodeling in hypertension and diabetes. These pathophysiological conditions drive glomerular vascular damage involving matrix metalloproteinases and their tissue inhibitors, gap junction proteins, and increase matrix formation. Increased matrix protein, such as collagen leads to glomerular-tubulointerstitial fibrosis and impairs renal function.

Kidney, in addition to its normal physiological function, also plays a major role in hydrogen sulfide (H2S) biosynthesis. Emerging evidences indicate that H2S is an important gaseous molecule with numerous physiological effects. In hypertension and diabetes pathophysiological kidney remodeling leads to diminished H2S biosynthesis, which further reduces renal outcome. We have focused our research to delineate whether increase of H2S to physiological level, either by drug or gene delivery, has any protective role in adverse renovascular remodeling and dysfunction during hypertension and diabetes.
Recent publications:

  1. Kundu S, Pushpakumar S, Khundmiri SJ, Sen U. Hydrogen sulfide mitigates hyperglycemic remodeling via liver kinase B1-adenosine monophosphate-activated protein kinase signaling. Biochim Biophys Acta. 2014 Aug 13. pii: S0167-4889(14)00304-8. doi: 10.1016/j.bbamcr.2014.08.005. PMID: 25127936.
  2. Pushpakumar SB, Kundu S, Sen U. Endothelial dysfunction: The link between homocysteine and hydrogen sulfide. Curr Med Chem. 2014 Jul 6. [Epub ahead of print] PMID: 25005183.
  3. Sen U, Pushpakumar SB, Amin MA, Tyagi SC. Homocysteine in renovascular complications: Hydrogen sulfide is a modulator and plausible anaerobic ATP generator. Nitric Oxide. 2014 Jun 22. pii: S1089-8603(14)00251-1. doi: 10.1016/j.niox.2014.06.006. PMID: 24963795.
  4. Pushpakumar SB, Kundu S, Metreveli N, Sen U. Folic Acid Mitigates Angiotensin-II-Induced Blood Pressure and Renal Remodeling. PLoS One. 2013 Dec 26;8(12):e83813. doi: 10.1371/journal.pone.0083813. PMID: 24386282.
  5. Pushpakumar SB, Kundu S, Metreveli N, Tyagi SC, Sen U. Matrix Metalloproteinase Inhibition Mitigates Renovascular Remodeling in Salt-Sensitive Hypertension. Physiol Rep. 2013 Aug 1;1(3):e00063. PMID: 24159376.
  6. Pushpakumar S, Kundu S, Pryor T, Givvimani S, Lederer E, Tyagi SC, Sen U. Angiotensin-II induced hypertension and renovascular remodelling in tissue inhibitor of metalloproteinase 2 knockout mice. J Hypertens. 2013 Nov;31(11):2270-81; discussion 2281. doi: 10.1097/HJH.0b013e3283649b33. PMID: 24077247.
  7. Kundu S, Pushpakumar SB, Tyagi A, Coley D, Sen U. Hydrogen sulfide deficiency and diabetic renal remodeling: role of matrix metalloproteinase-9. Am J Physiol Endocrinol Metab. 2013 Jun 15;304(12):E1365-78. doi: 10.1152/ajpendo.00604.2012. PMID: 23632630.
  8. 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; 303(1):C41-51. doi: 10.1152/ajpcell.00398.2011. PMID: 22517358.
  9. Givvimani S, Munjal C, Tyagi N, Sen U, Metreveli N, Tyagi SC. Mitochondrial division/mitophagy inhibitor (Mdivi) ameliorates pressure overload induced heart failure. PLoS One. 2012; 7(3):e32388. doi: 10.1371/journal.pone.0032388. PMID: 22479323.
  10. Basu P, Qipshidze N, Tyagi SC, Sen U. Remodeling in vein expresses arterial phenotype in hyperhomocysteinemia. Int J Physiol Pathophysiol Pharmacol. 2011; 3(4):266-79. PMID: 22162783.
  11. Basu P, Qipshidze N, Sen U, Givvimani S, Munjal C, Mishra PK, Tyagi SC. Chronic hyperhomocysteinemia causes vascular remodelling by instigating vein phenotype in artery. Arch Physiol Biochem. 2011; 117(5):270-82. doi: 10.3109/13813455.2011.599844. PMID: 21838575
  12. Sen U, Givvimani S, Abe OA, Lederer ED, Tyagi SC. Cystathionine β-synthase and cystathionine γ-lyase double gene transfer ameliorate homocysteine-mediated mesangial inflammation through hydrogen sulfide generation. Am J Physiol Cell Physiol. 2011; 300(1):C155-63. doi: 10.1152/ajpcell.00143.2010. PMID: 20943958.
  13. Mishra PK, Tyagi N, Sen U, Joshua IG, Tyagi SC. Synergism in hyperhomocysteinemia and diabetes: role of PPAR gamma and tempol. Cardiovasc Diabetol. 2010; 9:49. doi: 10.1186/1475-2840-9-49. PMID: 20828387.
  14. 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 postmyocardial infarction in mice. Am J Physiol Heart Circ Physiol. 2010; 299(5):H1484-93. doi: 10.1152/ajpheart.00577.2010. PMID: 20802128.
  15. Sen U, Tyagi SC. Homocysteine and Hypertension in Diabetes: Does PPARgamma Have a Regulatory Role? PPAR Res. 2010; 2010:806538. doi: 10.1155/2010/806538. PMID: 20613990.
  16. 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. 2010; 299(3):L301-11. doi: 10.1152/ajplung.00065.2010. PMID: 20581102.
  17. Sen U, Munjal C, Qipshidze N, Abe O, Gargoum R, Tyagi SC. Hydrogen sulfide regulates homocysteine-mediated glomerulosclerosis. Am J Nephrol. 2010; 31(5):442-55. doi: 10.1159/000296717. PMID: 20395677.
  18. Sen U, Mishra PK, Tyagi N, Tyagi SC. Homocysteine to hydrogen sulfide or hypertension. Cell Biochem Biophys. 2010 Jul;57(2-3):49-58. doi: 10.1007/s12013-010-9079-y. PMID: 20387006.
  19. Sen U, Basu P, Abe OA, Givvimani S, Tyagi N, Metreveli N, Shah KS, Passmore JC, Tyagi SC. Hydrogen sulfide ameliorates hyperhomocysteinemia-associated chronic renal failure. Am J Physiol Renal Physiol. 2009; 297(2):F410-9. doi: 10.1152/ajprenal.00145.2009. PMID: 19474193.
  20. Sen U, Tyagi N, Patibandla PK, Dean WL, Tyagi SC, Roberts AM, Lominadze D. Fibrinogen-induced endothelin-1 production from endothelial cells. Am J Physiol Cell Physiol. 2009; 296(4):C840-7. doi: 10.1152/ajpcell.00515.2008. PMID: 19193866.
  21. Sen U, Vacek TP, Hughes WM, Kumar M, Moshal KS, Tyagi N, Metreveli N, Hayden MR, Tyagi SC. Cardioprotective role of sodium thiosulfate on chronic heart failure by modulating endogenous H2S generation. Pharmacology. 2008;82(3):201-13. doi: 10.1159/000156486. PMID: 18810244.
  22. Sen U, Rodriguez WE, Tyagi N, Kumar M, Kundu S, Tyagi SC. Ciglitazone, a PPARgamma agonist, ameliorates diabetic nephropathy in part through homocysteine clearance. Am J Physiol Endocrinol Metab. 2008; 295(5):E1205-12. doi: 10.1152/ajpendo.90534.2008. PMID: 18780770.
  23. Kartha GK, Moshal KS, Sen U, Joshua IG, Tyagi N, Steed MM, Tyagi SC. Renal mitochondrial damage and protein modification in type-2 diabetes. Acta Diabetol. 2008 Jun;45(2):75-81. doi: 10.1007/s00592-008-0025-z. PMID: 18292963.

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