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The main focus of the Santhanam Lab is the cellular and molecular mechanisms of vascular stiffening in aging, hypertension, and pulmonary arterial hypertension, with a special emphasis on the crosstalk between matrix stiffness and vascular smooth muscle cell micromechanics and phenotype. Over the past decade, we have built a multidisciplinary team that comprises expertise in engineering, cell micromechanics, biochemistry, cell and molecular biology, vascular biology, tissue engineering, and medicine.

Lakshmi Santhanam is an Associate Professor of Anesthesiology and Critical Care Medicine, Biomedical Engineering, and Chemical and Biomolecular Engineering at the Johns Hopkins School of Medicine and Whiting School of Engineering. She has worked at the interface of engineering, cell biology, and medicine for the past decade and has made seminal contributions to our understanding of vascular stiffening in aging. The Santhanam lab has led the efforts to understand how matrix modifying enzymes, specifically tissue transglutaminase and lysyl oxidase like 2, drive vascular stiffening by dual mechanisms including matrix remodeling and vascular smooth muscle cell stiffening. Dr. Santhanam and her mentees are advancing the fields of matrix biology and vascular tissue biomechanics.

Jochen Steppan is a faculty member in the Department of Anesthesiology and CCM. He serves as the Director or Perioperative Medicine, High Risk Cardiovascular Disease and specializes in cardiothoracic anesthesiology for both adults and children. His research focuses on vascular stiffness of both the systemic and pulmonary vasculature. His research interest includes understanding the coupling of pulmonary artery remodeling and stiffening and right heart failure in pulmonary hypertension. He uses animal models of PAH to study mechanisms of pulmonary artery remodeling, and the benefits of targeting matrix remodeling to prevent or reverse vascular remodeling in PAH. Dr. Steppan is currently funded by a Society for Cardiovascular Anesthesiologists (SCA/IARS Mid-Career Grant) and an NIH K08 grant.

Sebastian Barreto-Ortiz is a postdoctoral fellow in the Department of Anesthesiology and CCM. His research interest is in the area harnessing of constitutively expressed non-visual opsins to mediate vasorelaxation to treat diseases characterized by chronic vasoconstriction. Dr. Barreto-Ortiz is funded by an AHA Postdoctoral Fellowship.

Huilei Wang is a PhD student in the Department of Biomedical Engineering. She is spearheading our efforts to identify the mechanisms by which the enzyme lysyl oxidase like 2 drives vascular stiffening in aging.

Sandeep Jandu is a pre-doctoral trainee with a keen interest in vascular physiology. He conducts a number of aging studies in the laboratory.

Kavitha Nandakumar received her Master of Philosophy from the University of Madras, India. Her research interest includes molecular genetics. She studies CRISPR/Cas9 generated mutations in mice and how they contribute to vascular stiffening in aging.

Joshua Krachman is an undergraduate student in the Department of Biomedical Engineering. He is currently funded by a Provost’s Undergraduate Research Award (PURA) to study the molecular mechanism of photorelaxation in the aorta.

Lydia Pak, Alan Poe, and Yurie Hong are undergraduate research trainees in the lab, that conduct hands-on research for various ongoing projects.

The Santhanam Lab investigates molecular and cellular mechanisms of vascular stiffening from “molecules to mice”. Current and recent work includes defining the role of the enzyme tissue transglutaminase (TG2) in vascular stiffening in aging. We have defined nitric oxide (NO) mediated TG2 regulation in the vasculature, the role of NO in TG2 trafficking, and a catalytically-dependent and catalytically-independent mechanisms of TG2 mediated vascular stiffening. Using the CRISPR/Cas9 technology, we have recently generated a new mouse model, the TG2-C277S mouse, that expresses a transamidation-deficient TG2.


In a second new area of research, we have defined a role for the amine oxidase lysyl oxidase like 2 (LOXL2) in vascular aging. Our studies show that LOXL2 mediates vascular stiffening by modulating Vascular smooth muscle cell stiffness and contractility. We have generated a number of novel cell lines and mouse models to further identify the specific mechanisms of LOXL2 regulation in the vasculature, the specific cellular source of LOXL2 in the aging vessel, and the mechanisms by which LOXL2 drives the stiffening of the vasculature.

The full list of publications can be found at: l&sort=date

1: Chan XY, Volkova E, Eoh J, Black R, Fang L, Gorashi R, Song J, Wang J, Elliott MB, Barreto-Ortiz SF, Chen J, Lin BL, Santhanam L, Cheng L, Lee FS, Prchal JT, Gerecht S. HIF2A gain-of-function mutation modulates the stiffness of smooth muscle cells and compromises vascular mechanics. iScience. 2021 Mar 2;24(4):102246. doi: 10.1016/j.isci.2021.102246. PMID: 33796838; PMCID: PMC7995528.

2: Fukunishi T, Ong CS, He YJ, Inoue T, Zhang H, Steppan J, Matsushita H, Johnson J, Santhanam L, Hibino N. Fast-degrading TEVGs Lead to Increased ECM Cross-linking Enzymes Expression. Tissue Eng Part A. 2021 Feb 18. doi: 10.1089/ten.TEA.2020.0266. Epub ahead of print. PMID: 33599167.

3: Steppan J, Jandu S, Savage W, Wang H, Kang S, Narayanan R, Nyhan D, Santhanam L. Restoring Blood Pressure in Hypertensive Mice Fails to Fully Reverse Vascular Stiffness. Front Physiol. 2020 Jul 21;11:824. doi: 10.3389/fphys.2020.00824. PMID: 32792976; PMCID: PMC7385310.

4: Steppan J, Jandu S, Wang H, Kang S, Savage W, Narayanan R, Nandakumar K, Santhanam L. Commonly used mouse strains have distinct vascular properties. Hypertens Res. 2020 Nov;43(11):1175-1181. doi: 10.1038/s41440-020-0467-4. Epub 2020 May 14. PMID: 32409775; PMCID: PMC7926191.

5: Mottard N, Berkowitz DE, Santhanam L. Assessing Renal Microvascular Reactivity by Laser Speckle-Contrast Imaging in Angiotensin-II-Treated Mice. Int J Nephrol Renovasc Dis. 2020 Mar 27;13:45-51. doi: 10.2147/IJNRD.S240147. PMID: 32273746; PMCID: PMC7108873.

6: Wang TY, Arking DE, Maleszewski JJ, Fox-Talbot K, Nieuwenhuis TO, Santhanam L, Virmani R, Rosenberg AZ, Halushka MK. Human cardiac myosin light chain 4 (MYL4) mosaic expression patterns vary by sex. Sci Rep. 2019 Sep 3;9(1):12681. doi: 10.1038/s41598-019-49191-0. PMID: 31481666; PMCID: PMC6722118.

7: Elliott MB, Ginn B, Fukunishi T, Bedja D, Suresh A, Chen T, Inoue T, Dietz HC, Santhanam L, Mao HQ, Hibino N, Gerecht S. Regenerative and durable small-diameter graft as an arterial conduit. Proc Natl Acad Sci U S A. 2019 Jun 25;116(26):12710-12719. doi: 10.1073/pnas.1905966116. Epub 2019 Jun 10. PMID: 31182572; PMCID: PMC6601275.

8: Steppan J, Wang H, Bergman Y, Rauer MJ, Tan S, Jandu S, Nandakumar K, Barreto-Ortiz S, Cole RN, Boronina TN, Zhu W, Halushka MK, An SS, Berkowitz DE, Santhanam L. Lysyl oxidase-like 2 depletion is protective in age-associated vascular stiffening. Am J Physiol Heart Circ Physiol. 2019 Jul 1;317(1):H49-H59. doi: 10.1152/ajpheart.00670.2018. Epub 2019 Apr 19. PMID: 31002285; PMCID: PMC6692735.

9: Greaney JL, Saunders EFH, Santhanam L, Alexander LM. Oxidative Stress Contributes to Microvascular Endothelial Dysfunction in Men and Women With Major Depressive Disorder. Circ Res. 2019 Feb 15;124(4):564-574. doi: 10.1161/CIRCRESAHA.118.313764. PMID: 30582458; PMCID: PMC6375800.

10: Armstrong DMF, Sikka G, Armstrong ADC, Saad KR, Freitas WR, Berkowitz DE, Fagundes DJ, Santhanam L, Taha MO. Knockdown of transglutaminase-2 prevents early age-induced vascular changes in mice1. Acta Cir Bras. 2018 Nov;33(11):991-999. doi: 10.1590/s0102 865020180110000006. PMID: 30517326.

11: Fukunishi T, Ong CS, Lui C, Pitaktong I, Smoot C, Harris J, Gabriele P, Vricella L, ­­, Lu S, Hibino N. Formation of Neoarteries with Optimal Remodeling Using Rapidly Degrading Textile Vascular Grafts. Tissue Eng Part A. 2019 Apr;25(7-8):632-641. doi: 10.1089/ten.TEA.2018.0167. Epub 2019 Jan 7. PMID: 30382009.

12 : McCarthy EK, Vakos A, Cottagiri M, Mantilla JJ, Santhanam L, Thomas DL, Amzel LM, Rose NR, Njoku DB. Identification of a Shared Cytochrome p4502E1 Epitope Found in Anesthetic Drug-Induced and Viral Hepatitis. mSphere. 2018 Oct 10;3(5):e00453-18. doi: 10.1128/mSphere.00453-18. Erratum in: mSphere. 2018 Dec 5;3(6):. Mantila, Joel J [corrected to Mantilla, Joel J]. PMID: 30305319; PMCID: PMC6180222.

13: Pandey D, Nomura Y, Rossberg MC, Hori D, Bhatta A, Keceli G, Leucker T, Santhanam L, Shimoda LA, Berkowitz D, Romer L. Hypoxia Triggers SENP1 (Sentrin- Specific Protease 1) Modulation of KLF15 (Kruppel-Like Factor 15) and Transcriptional Regulation of Arg2 (Arginase 2) in Pulmonary Endothelium. Arterioscler Thromb Vasc Biol. 2018 Apr;38(4):913-926. doi: 10.1161/ATVBAHA.117.310660. Epub 2018 Feb 22. PMID: 29472234; PMCID: PMC6738933.

14: Magruder JT, Grimm JC, Crawford TC, Johnston L, Santhanam L, Stephens RS, Berkowitz DE, Shah AS, Bush EL, Damarla M, Damico RL, Hassoun PM, Kim BS. Imatinib Is Protective Against Ischemia-Reperfusion Injury in an Ex Vivo Rabbit Model of Lung Injury. Ann Thorac Surg. 2018 Mar;105(3):950-956. doi:10.1016/j.athoracsur.2017.10.002. Epub 2017 Dec 28. PMID: 29289364.

15: Craighead DH, Wang H, Santhanam L, Alexander LM. Acute lysyl oxidase inhibition alters microvascular function in normotensive but not hypertensive men and women. Am J Physiol Heart Circ Physiol. 2018 Mar 1;314(3):H424-H433. doi: 10.1152/ajpheart.00521.2017. Epub 2017 Nov 22. PMID: 29167120; PMCID: PMC5899263.

16: Oh YS, Berkowitz DE, Cohen RA, Figueroa CA, Harrison DG, Humphrey JD, Larson DF, Leopold JA, Mecham RP, Ruiz-Opazo N, Santhanam L, Seta F, Shyy JYJ, Sun Z, Tsao PS, Wagenseil JE, Galis ZS. A Special Report on the NHLBI Initiative to Study Cellular and Molecular Mechanisms of Arterial Stiffness and Its Association With Hypertension. Circ Res. 2017 Nov 10;121(11):1216-1218. doi: 10.1161/CIRCRESAHA.117.311703. PMID: 29122942; PMCID: PMC5728161.

17: Stanhewicz AE, Jandu S, Santhanam L, Alexander LM. Alterations in endothelin type B receptor contribute to microvascular dysfunction in women who have had preeclampsia. Clin Sci (Lond). 2017 Nov 23;131(23):2777-2789. doi: 10.1042/CS20171292. PMID: 29042489; PMCID: PMC5922254.

18: Barreto Ortiz S, Hori D, Nomura Y, Yun X, Jiang H, Yong H, Chen J, Paek S, Pandey D, Sikka G, Bhatta A, Gillard A, Steppan J, Kim JH, Adachi H, Barodka VM, Romer L, An SS, Shimoda LA, Santhanam L, Berkowitz DE. Opsin 3 and 4 mediate light-induced pulmonary vasorelaxation that is potentiated by G protein-coupled receptor kinase 2 inhibition. Am J Physiol Lung Cell Mol Physiol. 2018 Jan 1;314(1):L93-L106. doi: 10.1152/ajplung.00091.2017. Epub 2017 Sep 7. PMID: 28882814; PMCID: PMC6335007.

19: Stanhewicz AE, Jandu S, Santhanam L, Alexander LM. Increased Angiotensin II Sensitivity Contributes to Microvascular Dysfunction in Women Who Have Had Preeclampsia. Hypertension. 2017 Aug;70(2):382-389. doi: 10.1161/HYPERTENSIONAHA.117.09386. Epub 2017 Jun 26. PMID: 28652473; PMCID: PMC5520653.

20: Greaney JL, Kutz JL, Shank SW, Jandu S, Santhanam L, Alexander LM. Impaired Hydrogen Sulfide-Mediated Vasodilation Contributes to Microvascular Endothelial Dysfunction in Hypertensive Adults. Hypertension. 2017 May;69(5):902-909. doi: 10.1161/HYPERTENSIONAHA.116.08964. Epub 2017 Mar 27. PMID: 28348008; PMCID: PMC5391285.

21: Hori D, Dunkerly-Eyring B, Nomura Y, Biswas D, Steppan J, Henao-Mejia J, Adachi H, Santhanam L, Berkowitz DE, Steenbergen C, Flavell RA, Das S. miR-181b regulates vascular stiffness age dependently in part by regulating TGF-ß signaling. PLoS One. 2017 Mar 21;12(3):e0174108. doi: 10.1371/journal.pone.0174108. PMID: 28323879; PMCID: PMC5360327.

22: Leucker TM, Nomura Y, Kim JH, Bhatta A, Wang V, Wecker A, Jandu S, Santhanam L, Berkowitz D, Romer L, Pandey D. Cystathionine ?-lyase protects vascular endothelium: a role for inhibition of histone deacetylase 6. Am J Physiol Heart Circ Physiol. 2017 Apr 1;312(4):H711 H720. doi: 10.1152/ajpheart.00724.2016. Epub 2017 Feb 10. PMID: 28188215; PMCID: PMC5407166.

23: Steppan J, Bergman Y, Viegas K, Armstrong D, Tan S, Wang H, Melucci S, Hori D, Park SY, Barreto SF, Isak A, Jandu S, Flavahan N, Butlin M, An SS, Avolio A, Berkowitz DE, Halushka MK, Santhanam L. Tissue Transglutaminase Modulates Vascular Stiffness and Function Through Crosslinking-Dependent and Crosslinking-Independent Functions. J Am Heart Assoc. 2017 Feb 3;6(2):e004161. doi: 10.1161/JAHA.116.004161. PMID: 28159817; PMCID: PMC5523743.

24: Aisenberg WH, Huang J, Zhu W, Rajkumar P, Cruz R, Santhanam L, Natarajan N, Yong HM, De Santiago B, Oh JJ, Yoon AR, Panettieri RA, Homann O, Sullivan JK, Liggett SB, Pluznick JL, An SS. Defining an olfactory receptor function in airway smooth muscle cells. Sci Rep. 2016 Dec 1;6:38231. doi: 10.1038/srep38231. PMID: 27905542; PMCID: PMC5131280.

25: Steppan J, Tran HT, Bead VR, Oh YJ, Sikka G, Bivalacqua TJ, Burnett AL, Berkowitz DE, Santhanam L. Arginase Inhibition Reverses Endothelial Dysfunction, Pulmonary Hypertension, and Vascular Stiffness in Transgenic Sickle Cell Mice. Anesth Analg. 2016 Sep;123(3):652-8. doi: 10.1213/ANE.0000000000001378. PMID: 27537757; PMCID: PMC5032625.

26: Oh YJ, Pau VC, Steppan J, Sikka G, Bead VR, Nyhan D, Levine BD, Berkowitz DE, Santhanam L. Role of tissue transglutaminase in age-associated ventricular stiffness. Amino Acids. 2017 Mar;49(3):695-704. doi: 10.1007/s00726-016-2295-z. Epub 2016 Jul 20. PMID: 27438265.

27: Kuo MM, Kim DH, Jandu S, Bergman Y, Tan S, Wang H, Pandey DR, Abraham TP, Shoukas AA, Berkowitz DE, Santhanam L. MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery. Am J Physiol Heart Circ Physiol. 2016 Jan 1;310(1):H71-9. doi: 10.1152/ajpheart.00574.2014. Epub 2015 Oct 30. PMID: 26519030; PMCID: PMC4796461.

28: Kutz JL, Greaney JL, Santhanam L, Alexander LM. Evidence for a functional vasodilatatory role for hydrogen sulphide in the human cutaneous microvasculature. J Physiol. 2015 May 1;593(9):2121-9. doi: 10.1113/JP270054. Epub 2015 Mar 25. PMID: 25639684; PMCID: PMC4422566.

29: Kuo MM, Barodka V, Abraham TP, Steppan J, Shoukas AA, Butlin M, Avolio A, Berkowitz DE, Santhanam L. Measuring ascending aortic stiffness in vivo in mice using ultrasound. J Vis Exp. 2014 Dec 2;(94):52200. doi: 10.3791/52200. PMID: 25489936; PMCID: PMC4354463

30: Sikka G, Hussmann GP, Pandey D, Cao S, Hori D, Park JT, Steppan J, Kim JH, Barodka V, Myers AC, Santhanam L, Nyhan D, Halushka MK, Koehler RC, Snyder SH, Shimoda LA, Berkowitz DE. Melanopsin mediates light-dependent relaxation in blood vessels. Proc Natl Acad Sci U S A. 2014 Dec 16;111(50):17977-82. doi: 10.1073/pnas.1420258111. Epub 2014 Nov 17. PMID: 25404319; PMCID: PMC4273372.

31: Mattison JA, Wang M, Bernier M, Zhang J, Park SS, Maudsley S, An SS, Santhanam L, Martin B, Faulkner S, Morrell C, Baur JA, Peshkin L, Sosnowska D, Csiszar A, Herbert RL, Tilmont EM, Ungvari Z, Pearson KJ, Lakatta EG, de Cabo R. Resveratrol prevents high fat/sucrose diet induced central arterial wall inflammation and stiffening in nonhuman primates. Cell Metab. 2014 Jul 1;20(1):183-90. doi: 10.1016/j.cmet.2014.04.018. Epub 2014 May 29. PMID: 24882067; PMCID: PMC4254394.

32: Steppan J, Sikka G, Jandu S, Barodka V, Halushka MK, Flavahan NA, Belkin AM, Nyhan D, Butlin M, Avolio A, Berkowitz DE, Santhanam L. Exercise, vascular stiffness, and tissue transglutaminase. J Am Heart Assoc. 2014 Apr 10;3(2):e000599. doi: 10.1161/JAHA.113.000599. PMID: 24721796; PMCID: PMC4187484.

33: Sikka G, Pandey D, Bhuniya AK, Steppan J, Armstrong D, Santhanam L, Nyhan D, Berkowitz DE. Contribution of arginase activation to vascular dysfunction in cigarette smoking. Atherosclerosis. 2013 Nov;231(1):91-4. doi: 10.1016/j.atherosclerosis.2013.08.026. Epub 2013 Sep 4. PMID: 24125417.

34: Weisbrod RM, Shiang T, Al Sayah L, Fry JL, Bajpai S, Reinhart-King CA, Lob HE, Santhanam L, Mitchell G, Cohen RA, Seta F. Arterial stiffening precedes systolic hypertension in diet-induced obesity. Hypertension. 2013 Dec;62(6):1105-10. doi: 10.1161/HYPERTENSIONAHA.113.01744. Epub 2013 Sep 23. PMID: 24060894; PMCID: PMC3951434.

35: Jung SM, Jandu S, Steppan J, Belkin A, An SS, Pak A, Choi EY, Nyhan D, Butlin M, Viegas K, Avolio A, Berkowitz DE, Santhanam L. Increased tissue transglutaminase activity contributes to central vascular stiffness in eNOS knockout mice. Am J Physiol Heart Circ Physiol. 2013 Sep 15;305(6):H803-10. doi: 10.1152/ajpheart.00103.2013. Epub 2013 Jul 19. PMID: 23873798; PMCID: PMC3761342.

36: Barodka V, Mohanty JG, Mustafa AK, Santhanam L, Nyhan A, Bhunia AK, Sikka G, Nyhan D, Berkowitz DE, Rifkind JM. Nitroprusside inhibits calcium-induced impairment of red blood cell deformability. Transfusion. 2014 Feb;54(2):434-44. doi: 10.1111/trf.12291. Epub 2013 Jun 19. PMID: 23781865.

37: Smith CJ, Santhanam L, Alexander LM. Rho-Kinase activity and cutaneous vasoconstriction is upregulated in essential hypertensive humans. Microvasc Res. 2013 May;87:58-64. doi: 10.1016/j.mvr.2013.02.005. Epub 2013 Feb 26. PMID: 23481864; PMCID: PMC4517969.

38: George TJ, Arnaoutakis GJ, Beaty CA, Jandu SK, Santhanam L, Berkowitz DE, Shah AS. A physiologic and biochemical profile of clinically rejected lungs on a normothermic ex vivo lung perfusion platform. J Surg Res. 2013 Jul;183(1):75-83. doi: 10.1016/j.jss.2012.11.012. Epub 2012 Nov 27. PMID: 23218735; PMCID: PMC4150088.

39: George TJ, Arnaoutakis GJ, Beaty CA, Jandu SK, Santhanam L, Berkowitz DE, Shah AS. Inhaled hydrogen sulfide improves graft function in an experimental model of lung transplantation. J Surg Res. 2012 Dec;178(2):593-600. doi: 10.1016/j.jss.2012.06.037. Epub 2012 Jun 27. PMID: 22771242; PMCID: PMC4131866.

40: Bruning RS, Santhanam L, Stanhewicz AE, Smith CJ, Berkowitz DE, Kenney WL, Holowatz LA. Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin. J Appl Physiol (1985). 2012 Jun;112(12):2019-26. doi: 10.1152/japplphysiol.01354.2011. Epub 2012 Apr 12. PMID: 22500004; PMCID: PMC3378394.

41: George TJ, Arnaoutakis GJ, Beaty CA, Jandu SK, Santhanam L, Berkowitz DE, Shah AS. Hydrogen sulfide decreases reactive oxygen in a model of lung transplantation. J Surg Res. 2012 Nov;178(1):494-501. doi: 10.1016/j.jss.2012.02.065. Epub 2012 Mar 18. PMID: 22464394; PMCID: PMC3389187.

42: Khan M, Steppan J, Schuleri KH, Ryoo S, Tuday E, Bugaj L, Santhanam L, Berkowitz T, Nyhan D, Shoukas AA, Berkowitz DE. Upregulation of arginase-II contributes to decreased age-related myocardial contractile reserve. Eur J Appl Physiol. 2012 Aug;112(8):2933-41. doi: 10.1007/s00421-011-2257-9. Epub 2011 Dec 8. Erratum in: Eur J Appl Physiol. 2012 Dec;112(12):4189. Schuleri, Karl [corrected to Schuleri, Karl H]. PMID: 22160208.

43: Santhanam L, Berkowitz DE, Belkin AM. Nitric oxide regulates non-classical secretion of tissue transglutaminase. Commun Integr Biol. 2011 Sep;4(5):584-6. doi: 10.4161/cib.4.5.16512. Epub 2011 Sep 1. PMID: 22046470; PMCID: PMC3204136.

44: Jandu SK, Webb AK, Pak A, Sevinc B, Nyhan D, Belkin AM, Flavahan NA, Berkowitz DE, Santhanam L. Nitric oxide regulates tissue transglutaminase localization and function in the vasculature. Amino Acids. 2013 Jan;44(1):261-9. doi: 10.1007/s00726-011-1090-0. Epub 2011 Oct 8. PMID: 21984378; PMCID: PMC3744185.

45: Smith CJ, Santhanam L, Bruning RS, Stanhewicz A, Berkowitz DE, Holowatz LA. Upregulation of inducible nitric oxide synthase contributes to attenuated cutaneous vasodilation in essential hypertensive humans. Hypertension. 2011 Nov;58(5):935-42. doi: 10.1161/HYPERTENSIONAHA.111.178129. Epub 2011 Sep 19.PMID: 21931069; PMCID: PMC3209704.

46: Dunn J, Gutbrod S, Webb A, Pak A, Jandu SK, Bhunia A, Berkowitz DE, Santhanam L. S-nitrosation of arginase 1 requires direct interaction with inducible nitric oxide synthase. Mol Cell Biochem. 2011 Sep;355(1-2):83-9. doi: 10.1007/s11010-011-0841-2. Epub 2011 May 1. PMID: 21533769; PMCID: PMC3744166.

47: Holowatz LA, Santhanam L, Webb A, Berkowitz DE, Kenney WL. Oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolaemic humans. J Physiol. 2011 Apr 15;589(Pt 8):2093-103. doi: 10.1113/jphysiol.2010.203935. Epub 2011 Feb 21. PMID: 21486801; PMCID: PMC3090606.

48: Santhanam L, Tuday EC, Webb AK, Dowzicky P, Kim JH, Oh YJ, Sikka G, Kuo M, Halushka MK, Macgregor AM, Dunn J, Gutbrod S, Yin D, Shoukas A, Nyhan D, Flavahan NA, Belkin AM, Berkowitz DE. Decreased S-nitrosylation of tissue transglutaminase contributes to age-related increases in vascular stiffness. Circ Res. 2010 Jul 9;107(1):117-25. doi: 10.1161/CIRCRESAHA.109.215228. Epub 2010 May 20. Erratum in: Circ Res. 2011 Apr  29;108(9):e12. PMID: 20489165.

49: Soucy KG, Lim HK, Attarzadeh DO, Santhanam L, Kim JH, Bhunia AK, Sevinc B, Ryoo S, Vazquez ME, Nyhan D, Shoukas AA, Berkowitz DE. Dietary inhibition of xanthine oxidase attenuates radiation-induced endothelial dysfunction in rat aorta. J Appl Physiol (1985). 2010 May;108(5):1250-8. doi: 10.1152/japplphysiol.00946.2009. Epub 2010 Feb 18. PMID: 20167676.

50: Kim JH, Bugaj LJ, Oh YJ, Bivalacqua TJ, Ryoo S, Soucy KG, Santhanam L, Webb A, Camara A, Sikka G, Nyhan D, Shoukas AA, Ilies M, Christianson DW, Champion HC, Berkowitz DE. Arginase inhibition restores NOS coupling and reverses endothelial dysfunction and vascular stiffness in old rats. J Appl Physiol (1985). 2009 Oct;107(4):1249-57. doi: 10.1152/japplphysiol.91393.2008. Epub 2009 Aug 6. PMID: 19661445; PMCID: PMC2763842.

51: Thompson-Torgerson CS, Champion HC, Santhanam L, Harris ZL, Shoukas AA. Cyclohexanone contamination from extracorporeal circuits impairs cardiovascular function. Am J Physiol Heart Circ Physiol. 2009 Jun;296(6):H1926-32. doi: 10.1152/ajpheart.00184.2009. Epub 2009 May 1. PMID: 19411286; PMCID: PMC2716145.

52: Santhanam L, Christianson DW, Nyhan D, Berkowitz DE. Arginase and vascular aging. J Appl Physiol (1985). 2008 Nov;105(5):1632-42. doi: 10.1152/japplphysiol.90627.2008. Epub 2008 Aug 21. PMID: 18719233; PMCID: PMC2584835.

53: Santhanam L, Gucek M, Brown TR, Mansharamani M, Ryoo S, Lemmon CA, Romer L, Shoukas AA, Berkowitz DE, Cole RN. Selective fluorescent labeling of S-nitrosothiols (S-FLOS): a novel method for studying S-nitrosation. Nitric Oxide. 2008 Nov;19(3):295-302. doi: 10.1016/j.niox.2008.07.007. Epub 2008 Jul 30. PMID: 18706513; PMCID: PMC3705760.

54: Ryoo S, Gupta G, Benjo A, Lim HK, Camara A, Sikka G, Lim HK, Sohi J, Santhanam L, Soucy K, Tuday E, Baraban E, Ilies M, Gerstenblith G, Nyhan D, Shoukas A, Christianson DW, Alp NJ, Champion HC, Huso D, Berkowitz DE  Endothelial arginase II: a novel target for the treatment of atherosclerosis. Circ Res. 2008 Apr 25;102(8):923-32. doi: 10.1161/CIRCRESAHA.107.169573. Epub 2008 Feb 28. PMID: 18309100.

55: Santhanam L, Lim HK, Lim HK, Miriel V, Brown T, Patel M, Balanson S, Ryoo S, Anderson M, Irani K, Khanday F, Di Costanzo L, Nyhan D, Hare JM, Christianson DW, Rivers R, Shoukas A, Berkowitz DE. Inducible NO synthase dependent S-nitrosylation and activation of arginase1 contribute to age-related endothelial dysfunction. Circ Res. 2007 Sep 28;101(7):692-702. doi: 10.1161/CIRCRESAHA.107.157727. Epub 2007 Aug 17. PMID: 17704205.

56: Kasuno K, Naqvi A, Dericco J, Yamamori T, Santhanam L, Mattagajasingh I, Yang S, Meyskens FL, Bosserhoff AK, Irani K. Antagonism of p66shc by melanoma inhibitory activity. Cell Death Differ. 2007 Aug;14(8):1414-21. doi: 10.1038/sj.cdd.4402131. Epub 2007 Apr 13. PMID: 17431427.

57: Soucy KG, Lim HK, Benjo A, Santhanam L, Ryoo S, Shoukas AA, Vazquez ME, Berkowitz DE. Single exposure gamma-irradiation amplifies xanthine oxidase activity and induces endothelial dysfunction in rat aorta. Radiat Environ Biophys. 2007 Jun;46(2):179-86. doi: 10.1007/s00411-006-0090-z. Epub 2007 Jan 26. PMID: 17256177.

58: Steppan J, Ryoo S, Schuleri KH, Gregg C, Hasan RK, White AR, Bugaj LJ, Khan M, Santhanam L, Nyhan D, Shoukas AA, Hare JM, Berkowitz DE. Arginase modulates myocardial contractility by a nitric oxide synthase 1-dependent mechanism. Proc Natl Acad Sci U S A. 2006 Mar 21;103(12):4759-64. doi: 10.1073/pnas.0506589103. Epub 2006 Mar 13. PMID: 16537391; PMCID: PMC1450243.

59: Khanday FA, Santhanam L, Kasuno K, Yamamori T, Naqvi A, Dericco J, Bugayenko A, Mattagajasingh I, Disanza A, Scita G, Irani K. Sos-mediated activation of rac1 by p66shc. J Cell Biol. 2006 Mar 13;172(6):817-22. doi: 10.1083/jcb.200506001. Epub 2006 Mar 6. PMID: 16520382; PMCID: PMC2063726.

60: Khanday FA, Yamamori T, Mattagajasingh I, Zhang Z, Bugayenko A, Naqvi A, Santhanam L, Nabi N, Kasuno K, Day BW, Irani K. Rac1 leads to phosphorylation- dependent increase in stability of the p66shc adaptor protein: role in Rac1-induced oxidative stress. Mol Biol Cell. 2006 Jan;17(1):122-9. doi: 10.1091/mbc.e05-06-0570. Epub 2005 Oct 26. PMID: 16251354; PMCID: PMC1345652.

61: Antoniotti S, Santhanam L, Ahuja D, Hogg MG, Dordick JS. Structural diversity of peroxidase catalyzed oxidation products of o-methoxyphenols. Org Lett. 2004 Jun 10;6(12):1975-8. doi: 10.1021/ol049448l. PMID: 15176797.

62: Johnson DK, Schillinger KJ, Kwait DM, Hughes CV, McNamara EJ, Ishmael F, O’Donnell RW, Chang MM, Hogg MG, Dordick JS, Santhanam L, Ziegler LM, Holland JA. Inhibition of NADPH oxidase activation in endothelial cells by ortho-methoxy-substituted catechols. Endothelium. 2002;9(3):191-203. doi: 10.1080/10623320213638. PMID: 12380644.

Dr. Lakshmi Santhanam
Department of Anesthesiology and Critical Care Medicine 
The Johns Hopkins Medical Institutions
720 Rutland Ave.
Ross 1150
Baltimore, MD 21205
[email protected]