Selected Publications

Academic Article

Year Title Altmetric
2020 Role of exosomal microRNA signatures: An emerging factor in preeclampsia-mediated cardiovascular disease.Placenta.  103:226-231. 2020
2020 Mythical metrics and methods: Needed paradigm shift in disease recognition and therapyMedical Hypotheses.  141. 2020
2020 Novel expression of GABAA receptors on resistance arteries that modulate myogenic toneJournal of Vascular Research.  57:113-125. 2020
2020 Late-onset renal hypertrophy and dysfunction in mice lacking CTRP1The FASEB Journal.  34:2657-2676. 2020
2020 Assessing renal microvascular reactivity by laser speckle-contrast imaging in angiotensin-II-treated mice 2020
2020 Biomimetic human small muscular pulmonary arteriesScience Advances.  6. 2020
2019 Histone deacetylase 6 inhibitor tubastatin A attenuates angiotensin II-induced hypertension by preventing cystathionine γ-lyase protein degradationPharmacological Research.  146. 2019
2019 Arginase II activity regulates cytosolic Ca2+ level in a p32-dependent manner that contributes to Ca2+-dependent vasoconstriction in native low-density lipoprotein-stimulated vascular smooth muscle cells 2019
2019 Airway smooth muscle photorelaxation via opsin receptor activation 2019
2019 Deletion of the microRNA-degrading nuclease, translin/trax, prevents pathogenic vascular stiffness 2019
2019 Editorial: Regulation of vascular function by circulating bloodFrontiers in Physiology.  10. 2019
2019 Effect of incubation with crystalloid solutions or medications on packed red blood cellsTransfusion.  59:2643-2651. 2019
2019 Lysyl oxidase-like 2 depletion is protective in age-associated vascular stiffening 2019
2018 Knockdown of transglutaminase-2 prevents early age-induced vascular changes in miceActa Cirurgica Brasileira.  33:991-999. 2018
2018 Ischemic Postconditioning and Milrinone 2018
2018 Arginase ii contributes to the Ca2+/CaMKII/eNOS axis by regulating Ca2+ concentration between the cytosol and mitochondria in a p32-dependent manner 2018
2018 Hypoxia Triggers SENP1 (Sentrin-Specific Protease 1) Modulation of KLF15 (Kruppel-Like Factor 15) and Transcriptional Regulation of Arg2 (Arginase 2) in Pulmonary Endothelium 2018
2018 Imatinib Is Protective Against Ischemia-Reperfusion Injury in an Ex Vivo Rabbit Model of Lung InjuryAnnals of Thoracic Surgery.  105:950-956. 2018
2018 Pulse wave travel distance as a novel marker of ventricular-arterial coupling 2018
2018 Relationship between the ambulatory arterial stiffness index and the lower limit of cerebral autoregulation during cardiac surgery 2018
2018 Opsin 3 and 4 mediate light-induced pulmonary vasorelaxation that is potentiated by G protein-coupled receptor kinase 2 inhibition 2018
2017 A pulse wave velocity based method to assess the mean arterial blood pressure limits of autoregulation in peripheral arteriesFrontiers in Physiology.  8. 2017
2017 Difference between ejection times measured at two different peripheral locations as a novel marker of vascular stiffnessPLoS ONE.  12. 2017
2017 Ejection time: Influence of hemodynamics and site of measurement in the arterial treeHypertension Research.  40:811-818. 2017
2017 The impact of posture on the cardiac depolarization and repolarization phases of the QT interval in healthy subjectsJournal of Electrocardiology.  50:640-645. 2017
2017 MiR-181b regulates vascular stiffness age dependently in part by regulating TGF-β signalingPLoS ONE.  12. 2017
2017 Role of tissue transglutaminase in age-associated ventricular stiffnessAmino Acids.  49:695-704. 2017
2017 Noninvasive assessment of the effect of position and exercise on pulse arrival to peripheral vascular beds in healthy volunteersFrontiers in Physiology.  8. 2017
2017 A special report on the NHLBI initiative to study cellular and molecular mechanisms of arterial stiffness and its association with hypertensionCirculation Research.  121:1216-1218. 2017
2017 Cystathionine γ-lyase protects vascular endothelium: A role for inhibition of histone deacetylase 6 2017
2017 Pilot study: Estimation of stroke volume and cardiac output from pulse wave velocityPLoS ONE.  12. 2017
2017 Tissue transglutaminase modulates vascular stiffness and function through crosslinking-dependent and crosslinking-independent functions 2017
2017 Validation of a real-time minute-to-minute urine output monitor and the feasibility of its clinical use for patients undergoing cardiac surgeryAnesthesia and Analgesia.  125:1883-1886. 2017
2016 Microbial short chain fatty acid metabolites lower blood pressure via endothelial G protein-coupled receptor 41Physiological Genomics.  48:826-834. 2016
2016 Arginase Inhibition Reverses Endothelial Dysfunction, Pulmonary Hypertension, and Vascular Stiffness in Transgenic Sickle Cell MiceAnesthesia and Analgesia.  123:652-658. 2016
2016 The Impact of Surgery and Stored Red Blood Cell Transfusions on Nitric Oxide HomeostasisAnesthesia and Analgesia.  123:274-282. 2016
2016 Hibernating squirrels: SIRTin clues for organ protection after ischemia-reperfusionAnesthesiology.  124:1215-1217. 2016
2016 Oxidative stress and rheologic properties of stored red blood cells before and after transfusion to surgical patientsTransfusion.  56:1101-1111. 2016
2016 2,3-Diphosphoglycerate Concentrations in Autologous Salvaged Versus Stored Red Blood Cells and in Surgical Patients after TransfusionAnesthesia and Analgesia.  122:616-623. 2016
2016 Role of senescence marker p16INK4a measured in peripheral blood T-lymphocytes in predicting length of hospital stay after coronary artery bypass surgery in older adultsExperimental Gerontology.  74:29-36. 2016
2016 MPST but not CSE is the primary regulator of hydrogen sulfide production and function in the coronary artery 2016
2016 Seeking a blood pressure-independent measure of vascular propertiesHypertension Research.  39:27-38. 2016
2016 The Effects of Hemodynamic Changes on Pulse Wave Velocity in Cardiothoracic Surgical PatientsBioMed Research International.  2016. 2016
2015 Inhibition of TLR4 attenuates vascular dysfunction and oxidative stress in diabetic rats 2015
2015 Subacute Hemolysis in Sickle Cell Mice Causes Priapism Secondary to NO Imbalance and PDE5 Dysregulation 2015
2015 NEDDylation promotes endothelial dysfunction: A role for HDAC2Journal of Molecular and Cellular Cardiology.  81:18-22. 2015
2015 Soluble guanylate cyclase is required for systemic vasodilation but not positive inotropy induced by nitroxyl in the mouseHypertension.  65:385-392. 2015
2014 Melanopsin mediates light-dependent relaxation in blood vessels 2014
2014 Measuring ascending aortic stiffness in vivo in mice using ultrasoundJournal of Visualized Experiments2014
2014 OxLDL Triggers Retrograde Translocation of Arginase2 in Aortic Endothelial Cells via ROCK and Mitochondrial Processing PeptidaseCirculation Research.  115:450-459. 2014
2014 Inhibition of glycosphingolipid synthesis ameliorates atherosclerosis and arterial stiffness in apolipoprotein E-/-Mice and rabbits fed a high-fat and -cholesterol dietCirculation.  129:2403-2413. 2014
2014 Effect of isoflurane on myocardial energetic and oxidative stress in cardiac muscle from Zucker diabetic fatty ratJournal of Pharmacology and Experimental Therapeutics.  349:21-28. 2014
2014 Exercise, vascular stiffness, and tissue transglutaminase. 2014
2014 Impaired red blood cell deformability after transfusion of stored allogeneic blood but not autologous salvaged blood in cardiac surgery patientsAnesthesia and Analgesia.  118:1179-1187. 2014
2014 New insights provided by a comparison of impaired deformability with erythrocyte oxidative stress for sickle cell diseaseBlood Cells, Molecules and Diseases.  52:230-235. 2014
2014 Nitroprusside inhibits calcium-induced impairment of red blood cell deformabilityTransfusion.  54:434-444. 2014
2014 Transcriptional regulation of endothelial arginase 2 by histone deacetylase 2 2014
2013 Contribution of arginase activation to vascular dysfunction in cigarette smokingAtherosclerosis.  231:91-94. 2013
2013 Development of novel arginase inhibitors for therapy of endothelial dysfunctionFrontiers in Immunology.  4. 2013
2013 Increased tissue transglutaminase activity contributes to central vascular stiffness in eNOS knockout mice 2013
2013 Sildenafil Citrate-Restored eNOS and PDE5 Regulation in Sickle Cell Mouse Penis Prevents Priapism Via Control of Oxidative/Nitrosative StressPLoS ONE.  8. 2013
2013 A physiologic and biochemical profile of clinically rejected lungs on a normothermic ex vivo lung perfusion platformJournal of Surgical Research.  183:75-83. 2013
2013 Arginase inhibition improves coronary microvascular function and reduces infarct size following ischaemia-reperfusion in a rat model 2013
2013 Decreased erythrocyte deformability after transfusion and the effects of erythrocyte storage durationAnesthesia and Analgesia.  116:975-981. 2013
2013 Sildenafil citrate protects skeletal muscle of ischemia-reperfusion injury. Immunohistochemical study in rat modelActa Cirurgica Brasileira.  28:282-287. 2013
2013 Interleukin 10 knockout frail mice develop cardiac and vascular dysfunction with increased ageExperimental Gerontology.  48:128-135. 2013
2013 Arginase II: atherogenesis beyond enzyme activity. 2013
2013 Nitric oxide regulates tissue transglutaminase localization and function in the vasculatureAmino Acids.  44:261-269. 2013
2012 Chronic oral administration of the arginase inhibitor 2(S)-amino-6-boronohexanoic Acid (ABH) improves erectile function in aged ratsJournal of Andrology.  33:1169-1175. 2012
2012 Erratum: Upregulation of arginase-II contributes to decreased age-related myocardial contractile reserve (European Journal of Applied Physiology (2012) 112 (2933-2941) DOI 10.1007/s00421-011-2257-9)European Journal of Applied Physiology.  112:4189. 2012
2012 Vasopressin-mediated enhancement of adrenergic vasoconstriction involves both the tyrosine kinase and the protein kinase C pathwaysAnesthesia and Analgesia.  115:1290-1295. 2012
2012 Hydrogen sulfide decreases reactive oxygen in a model of lung transplantationJournal of Surgical Research.  178:494-501. 2012
2012 Increased arginase II activity contributes to endothelial dysfunction through endothelial nitric oxide synthase uncoupling in aged mice 2012
2012 Alagebrium in combination with exercise ameliorates age-associated ventricular and vascular stiffnessExperimental Gerontology.  47:565-572. 2012
2012 About fACE: Perioperative use of angiotensin-converting enzyme inhibitorsCirculation.  126:249-251. 2012
2012 Endothelial nitric oxide synthase mediates cutaneous vasodilation during local heating and is attenuated in middle-aged human skin 2012
2012 Response to the letter by Edwards et alCirculation Research.  110. 2012
2012 Upregulation of arginase-II contributes to decreased age-related myocardial contractile reserveEuropean Journal of Applied Physiology.  112:2933-2941. 2012
2011 Hydrogen sulfide as endothelium-derived hyperpolarizing factor sulfhydrates potassium channelsCirculation Research.  109:1259-1268. 2011
2011 Vascular stiffness and increased pulse pressure in the aging cardiovascular systemCardiology Research and Practice.  1. 2011
2011 HZE 56Fe-ion irradiation induces endothelial dysfunction in rat aorta: Role of xanthine oxidaseRadiation Research.  176:474-485. 2011
2011 S-Nitrosation of arginase 1 requires direct interaction with inducible nitric oxide synthase 2011
2011 Endothelial arginase II and atherosclerosisKorean Journal of Anesthesiology.  61:3-11. 2011
2011 Phosphodiesterase-5A (PDE5A) is localized to the endothelial caveolae and modulates NOS3 activityCardiovascular Research.  90:353-363. 2011
2011 Oral atorvastatin therapy restores cutaneous microvascular function by decreasing arginase activity in hypercholesterolaemic humans 2011
2011 Restoring leptin signaling reduces hyperlipidemia and improves vascular stiffness induced by chronic intermittent hypoxia 2011
2011 OxLDL-dependent activation of arginase II is dependent on the LOX-1 receptor and downstream RhoA signalingAtherosclerosis.  214:279-287. 2011
2011 Implications of vascular agingAnesthesia and Analgesia.  112:1048-1060. 2011
2011 Upregulation of inducible nitric oxide synthase contributes to attenuated cutaneous vasodilation in essential hypertensive humans.Hypertension.  58:935-942. 2011
2010 Early changes in vasoreactivity after simulated microgravity are due to an upregulation of the endothelium-dependent nitric oxide/cGMP pathwayEuropean Journal of Applied Physiology.  110:395-404. 2010
2010 Single exposure to radiation produces early anti-angiogenic effects in mouse aortaRadiation and Environmental Biophysics.  49:397-404. 2010
2010 Increased endothelial exocytosis and generation of endothelin-1 contributes to constriction of aged arteriesCirculation Research.  107:242-251. 2010
2010 Decreased S-nitrosylation of tissue transglutaminase contributes to age-related increases in vascular stiffnessCirculation Research.  107:117-125. 2010
2010 Dietary inhibition of xanthine oxidase attenuates radiation-induced endothelial dysfunction in rat aorta 2010
2010 Effect of intermittent hypoxia on atherosclerosis in apolipoprotein E-deficient miceAtherosclerosis.  209:381-386. 2010
2010 Leptin is essential in maintaining normal vascular compliance independent of body weightInternational Journal of Obesity.  34:203-206. 2010
2010 β2-adrenergic receptor-coupled phosphoinositide 3-kinase constrains cAMP-dependent increases in cardiac inotropy through phosphodiesterase 4 activationAnesthesia and Analgesia.  111:870-877. 2010
2009 Arginase inhibition restores NOS coupling and reverses endothelial dysfunction and vascular stiffness in old rats 2009
2009 Simulated microgravity-induced aortic remodeling 2009
2009 Sildenafil Inhibits Superoxide Formation and Prevents Endothelial Dysfunction in a Mouse Model of Secondhand Smoke Induced Erectile Dysfunction 2009
2009 Increased oxidant activity mediates vascular dysfunction in vibration injuryJournal of Pharmacology and Experimental Therapeutics.  328:223-230. 2009
2008 Arginase and vascular aging 2008
2008 Selective fluorescent labeling of S-nitrosothiols (S-FLOS): A novel method for studying S-nitrosationNitric Oxide: Biology and Chemistry.  19:295-302. 2008
2008 Endothelial arginase II: A novel target for the treatment of atherosclerosisCirculation Research.  102:923-932. 2008
2008 Perioperative blood pressure management: Does central vascular stiffness matter?Anesthesia and Analgesia.  107:1103-1106. 2008
2007 Mitochondrial arginase II constrains endothelial NOS-3 activity 2007
2007 Pulse pressure is an age-independent predictor of stroke development after cardiac surgeryHypertension.  50:630-635. 2007
2007 Inducible NO synthase-dependent S-nitrosylation and activation of arginase1 contribute to age-related endothelial dysfunctionCirculation Research.  101:692-702. 2007
2007 Microgravity and cardiac atrophy: No sex discrimination 2007
2007 Microgravity-induced changes in aortic stiffness and their role in orthostatic intolerance 2007
2007 Myocyte nitroso-redox imbalance in sepsis: NO simple answerCirculation Research.  100:1-4. 2007
2006 Impaired shear stress-induced nitric oxide production through decreased NOS phosphorylation contributes to age-related vascular stiffness 2006
2006 Oxidized low-density lipoprotein-dependent endothelial arginase II activation contributes to impaired nitric oxide signalingCirculation Research.  99:951-960. 2006
2006 Response to does arginase activity in vitro represent that in vivo? [2]Hypertension.  48. 2006
2006 Arginase modulates myocardial contractility by a nitric oxide synthase 1-dependent mechanism 2006
2006 Activation of the cardiac ciliary neurotrophic factor receptor reverses left ventricular hypertrophy in leptin-deficient and leptin-resistant obesity 2006
2006 Knockdown of arginase I restores NO signaling in the vasculature of old ratsHypertension.  47:245-251. 2006
2006 Cardiac myocyte apoptosis is associated with increased DNA damage and decreased survival in murine models of obesityCirculation Research.  98:119-124. 2006
2005 P66shc regulates endothelial NO production and endothelium-dependent vasorelaxation: Implications for age-associated vascular dysfunctionJournal of Molecular and Cellular Cardiology.  39:992-995. 2005
2005 Simulated microgravity produces attenuated baroreflex-mediated pressor, chronotropic, and inotropic responses in mice 2005
2005 Leptin repletion restores depressed β-adrenergic contractility in ob/ob mice independently of cardiac hypertrophy 2005
2004 Neuronal nitric oxide synthase negatively regulates xanthine oxidoreductase inhibition of cardiac excitation-contraction coupling 2004
2004 Critical role for the α-1B adrenergic receptor at the sympathetic neuroeffector junctionHypertension.  44:776-782. 2004
2004 Apurinic/apyrmidinic endonuclease 1 regulates endothelial NO production and vascular toneCirculation Research.  95:902-910. 2004
2004 Enhanced vasodilatory responses to milrinone in catecholamine-precontracted small pulmonary arteriesAnesthesia and Analgesia.  98:1618-1622. 2004
2003 Arginase Reciprocally Regulates Nitric Oxide Synthase Activity and Contributes to Endothelial Dysfunction in Aging Blood VesselsCirculation.  108:2000-2006. 2003
2003 Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in miceCirculation.  108:754-759. 2003
2003 Nitric oxide regulation of myocardial contractility and calcium cycling: Independent impact of neuronal and endothelial nitric oxide synthasesCirculation Research.  92:1322-1329. 2003
2002 Nitric oxide regulates the heart by spatial confinement of nitric oxide synthase isoformsNature.  416:337-340. 2002
2002 Estrogen has opposing effects on vascular reactivity in obese, insulin-resistant male Zucker rats 2002
2002 Impaired pulmonary artery contractile responses in a rat model of microgravity: Role of nitric oxide 2002
2001 Differential gene expression in a murine model of cancer cachexia 2001
2001 Hindlimb unweighting affects rat vascular capacitance function 2001
2001 Overview of the perioperative management of the patient with primary pulmonary hypertensionProblems in Anesthesia.  13:224-239. 2001
2001 Weight loss is not associated hyperleptinemia in humans pancreatic cancerJournal of Clinical Endocrinology and Metabolism.  86:162-166. 2001
2000 Endogenous circulating sympatholytic factor in orthostatic intoleranceHypertension.  36:553-560. 2000
2000 Reduction of obesity, as induced by leptin, reverses endothelial dysfunction in obese (Lep(ob)) mice 2000
2000 The effects of hindlimb unweighting on the capacitance of rat small mesenteric veins 2000
2000 β3-adrenoceptor deficiency blocks nitric oxide-dependent inhibition of myocardial contractilityJournal of Clinical Investigation.  106:697-703. 2000
1999 Subtype specific regulation of human vascular α1-adrenergic receptors by vessel bed and ageCirculation.  100:2336-2343. 1999
1999 Pulmonary vascular endothelial responses are differentially modulated after cardiopulmonary bypassJournal of Cardiovascular Pharmacology.  34:518-525. 1999
1999 Brachydactyly type B with its distinct facies and 'cooks syndrome' are the same entityClinical Dysmorphology.  8:41-45. 1999
1999 Effect of leptin deficiency on metabolic rate in ob/ob mice 1999
1999 Leptin prevents respiratory depression in obesityAmerican Journal of Respiratory and Critical Care Medicine.  159:1477-1484. 1999
1999 Molecular biology in cardiovascular anesthesiology: The brave new frontier 1999
1998 Endotoxin-induced alteration in the expression of leptin and β3-adrenergic receptor in adipose tissueAmerican Journal of Physiology.  274. 1998
1998 Endotoxin-induced alteration in the expression of leptin and β3- adrenergic receptor in adipose tissue 1998
1997 Endotoxin induced transcriptional regulation of leptin and beta-3 adrenergic receptor (b3AR) in mouse adipose tissueThe FASEB Journal.  11. 1997
1997 Beta-3 adrenoceptor (beta-3AR) expression in leptin treated ob/ob miceLife Sciences.  61:59-64. 1997
1996 Role of the β3-adrenergic receptor locus in obesity and noninsulin- dependent diabetes among members of Caucasian families with a diabetic sibling pairJournal of Clinical Endocrinology and Metabolism.  81:4422-4427. 1996
1996 Hypotension resistant to therapy with α receptor agonists complicating cardiopulmonary bypass: Lithium as a potential causeAnesthesia and Analgesia.  82:1082-1085. 1996
1995 Distribution of β3-adrenoceptor mRNA in human tissues 1995
1995 Constitutive Nitric Oxide Synthase Is Expressed and Nitric Oxide-Mediated Relaxation Is Preserved in Retrieved Human Aortocoronary Vein GraftsJournal of Surgical Research.  58:732-738. 1995
1994 Expression of α1-adrenergic receptor subtype mRNA in rat tissues and human SK-N-MC neuronal cells: Implications for α1-adrenergic receptor subtype classificationMolecular Pharmacology.  46:221-226. 1994
1994 Localization of mRNA for three distinct α1-adrenergic receptor subtypes in human tissues: Implications for human α-adrenergic physiologyMolecular Pharmacology.  45:171-175. 1994
1994 Endothelins: Biochemistry and pathophysiologic actionsAnesthesiology.  80:892-905. 1994
1994 Localization of messenger RNA for three distinct α2-adrenergic receptor subtypes in human tissues: Evidence for species heterogeneity and implications for human pharmacologyAnesthesiology.  81:1235-1244. 1994


Year Title Altmetric
2018 Pharmacology of Anesthetic Drugs.  112-131. 2018
2010 The disappearing left ventricle: A double lung transplant in a patient with severe pulmonary hypertension.  391-396. 2010

Research Overview

  • Basic and Translational Research:
    My laboratory has been studying the mechanisms contributing to the pathobiology of vascular dysfunction in diseases such as age related systolic hypertension, atherosclerosis, radiation and pulmonary hypertension for the last 17 years. This integrated vascular biology laboratory has been continuously funded for 13 years by the NIH, as well as the American Heart Association and NASA through the National Space Biomedical Research Institute. Our vascular research program has attracted undergraduates, from the Johns Hopkins Homewood campus as a result of my joint appointment in the Dept. of Biomedical Engineering. We have also been fortunate to attract and train both Masters and PhD students. and train both MD and PhD Post-doctoral fellows, from the Departments of Anesthesiology, Cardiology and Pulmonary Medicine at Hopkins, and from around the country and the world. Many of the graduate and post-doctoral fellows have received funding through foundations such as the AHA and the Foundation for Anesthesia Education and Research (FAER). The majority of mentees have gone on to productive and successful careers in academic medicine, basic and translational science, and industry. It is our goal to continue to train the best academicians in cardiovascular biology such that this next generation of clinician and basic scientists will be able to address the medical needs and challenges of the rising cardiovascular burden. Our major contributions to science include 1) Arginase 1 and its contribution to age-related endothelial dysfunction and vascular stiffness. We were the first to demonstrate that arginase in endothelial cells reciprocally regulates nitric oxide production leading to eNOS uncoupling and endothelial dysfunction and vascular disease. This has led to the emergence of a robust literature on arginase upregulation and vascular disease. It has also led to the development of small molecule inhibitors of arginase for therapy of diseases in which endothelial dysfunction is a significant component. 2) Arginase 2 as a novel target in atherosclerosis: As with age-related endothelial dysfunction we described the mechanisms by which upregulation of arginase 2 by atherogenic stimuli such a as OxLDL through the Lox-1 receptor contributes to atherosclerosis. 3) Radiation induced vascular dysfunction: With funding from NASA and the National Space Biomedical Research Institution (through NASA) to explore the role of Galactic cosmic radiation in the context of space flight beyond low earth orbit, we explored the mechanisms of radiation induced endothelial injury and potential countermeasures to attenuate it. Using both conventional gamma radiation and high linear energy transfer radiation (using the NASA Research laboratory beamline at Brookhaven National Labs, Long Island) we determined the importance of Xanthine oxidase as a producer of radiation -induced oxidative stress and dysfunction in the endothelium. 4) Role of tissue transglutaminase (TG2) and other cross-linking matrix enzymes in Age-related vascular stiffness: Vascular stiffness and resultant age-dependent systolic hypertension remains an independent risk factor in cardiovascular disease. The molecular mechanisms underlying vascular stiffness remain incompletely understood. We have identified impaired nitric oxide bioavailability as an important contributor to vascular stiffness. Nitric oxide not only regulates vascular function through alterations in vascular tone but modifies the function of enzymes and other proteins by redox-dependent modification, S-nitrosylation. We have demonstrated that impaired NO bioavailability enhance the activity of the cross-linking enzyme tissue transglutaminase (TG2) which in turn contributes to increases in vascular stiffness. Using a secretome proteomic approach we have identified other enzymes that might contribute to age-related vascular stiffness: 5) Role of Opsins in the regulation of photorelaxation and vascular function: Classic sensory receptors in extrasensory sites and their roles in signal transduction: In a serendipitous finding we have discovered a light activated non-visual opsin, melanopsin (opsin 4 (Opn4))-dependent vasorelaxant pathway which in the presence of a beta adrenergic receptor kinase 1 (ARK 1 or GRK2) inhibitor is profoundly amplified. We have thus characterized an endogenous opsin-mediated, light-activated molecular switch for vasorelaxation that can be targeted for therapy in all diseases in which altered vasoreactivity is a significant pathophysiologic contributor.
    All of these contribution have been or are funded by independent R01’s except for the radiation work which was funded by NASA and the National Space Biomedical Research Institution.

    Clinical Research:
    1) Age-related vascular stiffness and outcomes: As we age, our large conduit vessels (aorta) become stiffer, a process that leads to systolic hypertension. This vascular stiffness is and independent predictor of MACE. While this has been show in the context of patients following MI, stroke and renal dysfunction, the role of vascular stiffness as a predictor of peri-operative outcome has not been explored. Moreover, while chronologic age is immutable, vascular age is modifiable. Using newly developed devices and technique we continue to study the role of vascular stiffness in peri-operative outcomes and explore interventions that might improve vascular “age” and thus peri-operative outcomes.
    2) Red cell health and transfusion: While transfusion is associated with adverse outcomes, the mechanisms underpinning is incompletely understood. Using multiple measures of erythrocyte health including RBC deformability, oxidative stress, NO we continue to explore the effect of storage duration on these metrics.
  • Education And Training

  • Bachelor of Medicine & Surgery (MBBS), University of the Witwatersrand 1984
  • Long Island Jewish Medical Center, Internship 1989
  • Coronation Hospital, Internship 1985
  • Duke Medical Center Anesthesia, Residency 1992
  • Duke Medical Center Cardiac Anesthesia, Postdoctoral Fellowship 1993
  • Long Island Jewish Medical Center Microbiology, Postdoctoral Fellowship 1988
  • South African Institute for Medical Research, Postdoctoral Fellowship 1987
  • Full Name

  • Dan Berkowitz