Zoltan Ungvari, MD, PhD

Zoltan Ungvari

Professor, Donald W. Reynolds Chair of Aging Research

Contact

University of Oklahoma Health Sciences Center
975 NE 10th Street   BRC 1315A
Oklahoma City, OK 73104
Telephone: (405) 271-8000 ext. 47809
Email: zoltan-ungvari@ouhsc.edu

Education

M.D., 1996   Semmelweis University, Budapest, Hungary
Ph.D., 2001  Semmelweis University, Budapest, Hungary
American Heart Association Post-doctoral fellowship, New York Medical College, Valhalla, NY

Research Interests

  • Cardiovascular Aging
  • Vascular Biology
  • Free Radical Biology
  • Comparative Biology of Aging

Research in Dr. Ungvári's laboratory is focused on vascular physiology and cell biology with an emphasis on oxidative stress and inflammation.

Active areas of research include:

  1. Molecular biology of cardiovascular aging: 
    Aging-related cardiovascular diseases are the greatest health challenge the U.S. faces in the 21st century. We aim to understand the mechanisms underlying age-related deterioration of vascular and cardiac function and identify novel therapeutic targets to delay/prevent the deleterious effects of cardiovascular aging  (mitochondrial biogenesis, mitochondrial oxidative stress, NADPH oxidase-dependent signaling, pro-inflammatory mechanisms, GH/IGF-1 system, etc).
  2. Cardiovascular protection by caloric restriction and caloric restriction mimics:
    There is an urgent need to develop novel interventional treatments for promotion of cardiovascular health in older persons. The dietary regimen known as caloric restriction can delay aging and extend lifespan in evolutionary distant organisms. A major goal of Dr. Ungvári's laboratory is to identify novel mechanisms induced by caloric restriction that act as regulators of vascular redox homeostasis and thus suppress oxidative stress and oxidative stress-induced inflammatory processes in aging and target them using a pharmacological approach to promote vascular health.
  3. Comparative aging studies: 
    Mammalian lifespan ranges hundred-fold and long-living species may be useful models for successful cardiovascular aging in humans. Comparative studies exploiting the large differences in maximum lifespan potential and cardiovascular aging patterns are particularly relevant. Dr. Ungvári's laboratory compares mechanisms related to oxidative stress, oxidative stress resistance and redox signaling between long-living species and shorter-living ones to elucidate key mechanisms for delaying cardiovascular aging.
  4. Hemodynamic forces and vascular inflammation: 
    Atherosclerosis develops in hemodynamically well-defined regions. BMPs are novel TGFβ family member cytokines that play a crucial role in development. Recently, BMPs have been discovered in adult blood vessels and have been linked to atherogenesis and vascular calcification. Studies in Dr. Ungvári's laboratory suggest that BMP2 is up-regulated by high pressure, oxidative stress and inflammatory cytokines, whereas the vascular expression of BMP4, a structurally releated cytokine is regulated by wall shear stress. The aforementione studies have shown that BMP2/4 elicits endothelial activation increasing monocyte adhesiveness, endothelial dysfunction and oxidative stress. Dr. Ungvári's laboratory aims to understand i) the transcriptional regulation of BMPs and other cytokines by hemodynamic forces in endothelial cells, and ii) the pathophysiological role of BMPs in vascular diseases.

Dr. Ungvári has published more than 90 original manuscripts and invited reviews, served on the Vascular Biology and Blood Pressure Regulation study section of the American Heart Association and has been invited to present his research at national and international meetings.

Recent Publications

  1. Ungvari Z, Tucsek Z, Sosnowska D, Toth P, Gautam T, Podlutsky A, Csiszar A, Losonczy G, Valcarcel-Ares M, Sonntag WE, Csiszar A. Aging-Induced Dysregulation of Dicer1-Dependent MicroRNA Expression Impairs Angiogenic Capacity of Rat Cerebromicrovascular Endothelial Cells. J Gerontol A Biol Sci Med Sci 2012 Dec 13. (FULL TEXT)
  2. Tucsek Z, Gautam T, Sonntag WE, Toth P, Saito H, Salomao R, Szabo C, Csiszar A, Ungvari Z. Aging Exacerbates Microvascular Endothelial Damage Induced by Circulating Factors Present in the Serum of Septic Patients. J Gerontol A Biol Sci Med Sci 2012 Nov 26. (FULL TEXT)
  3. Ungvari Z, Sosnowska D, Mason JB, Gruber H, Lee SW, Schwartz TS, Brown MK, Storm NJ, Fortney K, Sowa J, Byrne AB, Kurz T, Levy E, Sonntag WE, Austad SN, Csiszar A, Ridgway I. Resistance to Genotoxic Stresses in Arctica islandica, the Longest Living Noncolonial Animal: Is Extreme Longevity Associated With a Multistress Resistance Phenotype? J Gerontol A Biol Sci Med Sci 2012 Oct 10. (FULL TEXT)
  4. Csiszar A, Labinskyy N, Smith K, Rivera A, Orosz Z, Ungvari Z, Vasculoprotective effects of anti-TNFα treatment in aging Am J Pathology 2007;170(1):388-698
  5. Stef G, Csiszar A, Ungvari Z, Veress G. Inhibition of NAD(P)H Oxidase Attenuates Aggregation of Platelets from High-risk Cardiac Patients with Aspirin Resistance Pharmacol Reports 2007 (in press)
  6. Orosz Z, Csiszar A, Labinskyy N, Smith KE, Rivera A, Kaminski PM, Ferdinandy P, Wolin MS, Ungvari Z.: Cigarette smoke-induced proinflammatory alterations in the endothelial phenotype: role of NAD(P)H oxidase activation. Am J Physiol 2007;292(1):H130-9.
  7. Csiszar A, Toth J, Peti-Peterdi J, Ungvari Z. The aging kidney: role of endothelial oxidative stress and inflammation. Acta Physiol Hung. 2007 Mar;94(1-2):107-15.
  8. Csiszar A, Labinskyy N, Smith KE, Rivera A, Bakker ENTP, Jo H, Gardner J, Orosz Z,Ungvari Z.: Down-regulation of BMP-4 Expression in Coronary Arterial Endothelial Cells: Role of Shear Stress and the cAMP/PKA Pathway; Arterioscler Thromb Vasc Biol 2007; 27(4):776-82.
  9. Ungvari Z, Orosz Z, Rivera A, Labinskyy N, Xiangmin Z, Csiszar A: Resveratrol Increases Vascular Oxidative Stress Resistance  Am J Physiol 2007;292:H2417-H2424
  10. Ungvari Z, Orosz Z, Labinskyy N, Rivera A, Xiangmin Z, Smith K, Csiszar A, Increased mitochondrial H2O2 production promotes endothelial NF-?B activation in aged rat arteries Am J Physiol 2007;293:H37-H47
  11. Batkai S, Rajesh M, Mukhopadhyay P, Hasko G, Liaudet L, Cravatt BF, Csiszar A, Ungvari Z, Pacher P. Decreased age-related cardiac dysfunction, myocardial nitrative stress, inflammatory gene expression and apoptosis in mice lacking fatty acid amide hydrolase. Am J Physiol Heart Circ Physiol. 2007;293:H909-918 
  12. Ballabh P, Xu H, Hu F, Braun A, Smith K, Rivera A, Lou N, Ungvari Z, Goldman S, Csiszar A, Nedergaard M. Angiogenic Inhibition Reduces Germinal Matrix Hemorrhage. Nature Medicine 2007 Apr;13(4):477-485.
  13. Csiszar A, Labinskyy N, Orosz Z, Buffenstein R, Ungvari Z: Vascular aging in the longest-living rodent, the naked mole-rat Am J Physiology 2007;293:H919-927
  14. Csiszar A, Labinskyy N, Xiangmin Z, Austad SN, Podlutsky A, Ungvari Z: Endothelial O2.-  and H2O2 production and vascular oxidative stress resistance in two closely related rodent species with disparate longevity Aging Cell 2007 Dec;6(6):783-97.
  15. Rajesh M, Mukhopadhyay P, Batkai S, Hasko G, Liaudet L, Huffman J, Csiszar A,Ungvari Z, Mackie K, Chatterjee S, Pacher P: CB-2 receptor stimulation attenuates TNFα-induced endothelial activation, transendothelial migration of monocytes and monocyte-endothelial adhesion. Am J Physiology 2007;293(4):H2210-8.
  16. Ungvari Z. Endothelium-derived bone morphogenic protein (BMP) antagonists may counteract the pro-atherogenic vascular effects of BMP4. Circulation 2007 116(11):1221-3
  17. Braun A, Xu H, Hu F, Kocherlakota P, Siegel D, Chander P, Ungvari Z, Csiszar A, Nedergaard M, Ballabh P: Paucity of Pericytes in Germinal matrix Vasculature of Premature Infants. J Neurosci 2007 Oct 31;27(44):12012-24.
  18. Xu H, Hu F, Sado Y, Ninomiya Y, Borza DB, Ungvari Z, LaGamma E, Csiszar A, Nedergaard M, Ballabh P: Maturational Changes in Laminin, Fibronectin, Collagen IV and Perlecan in Germinal Matrix, Cortex and White Matter, and Effect of Betamethasone. J Neurosci Res 2008;86(7):1482-500
  19. Pearson KJ, Lewis KN, Price NL, Chang JW, Perez E, Cascajo MV, Tamashiro KL, Poosala S, Csiszar A, Ungvari Z, Kensler TW, Yamamoto M, Egan JM, Longo DL, Ingram DK, Navas P, de Cabo R: Nrf2 Mediates Cancer Protection but not Prolongevity Induced by Caloric Restriction. PNAS 2008;105(7):2325-30
  20. Pacher P, Ungvari Z: Pleiotropic effects of the CB2 cannabinoid receptor activation on human monocyte migration: implications for atherosclerosis and inflammatory diseases. Am J Physiol 2008 ;294(3):H1133-4
  21. Ungvari Z, Buffenstein R, Austad SN, Podlutsky A, Kaley G, Csiszar A: Oxidative stress in vascular senescence: lessons from successfully aging species. Frontiers Biosci 2008 1;13:5056-70.
  22. Ungvari Z, Parrado-Fernandez C, Csiszar A, de Cabo R: Mechanisms underlying caloric restriction and life span regulation: implications for vascular aging. Circ Res 2008;102(5):519-28.
  23. Ungvari Z, Labinskyy N, Gupte SA, Chander PN, Edwards JG, Csiszar A. Dysregulation of mitochondrial biogenesis in vascular endothelial and smooth muscle cells of aged rats. Am J Physiol Heart Circ Physiol. 2008;294(5):H2121-8. 
  24. Ungvari Z, Krasnikov B, Csiszar A, Labinskyy N, Mukhopadhyay P, Pacher P, Cooper AJL, Podlutskaya N, Austad SN, Podlutsky A. Testing hypotheses of aging in long-lived mice of the genus Peromyscus: association between longevity and mitochondrial stress resistance, ROS detoxification pathways and DNA repair efficiency. AGE 2008;30(2-3):121-33.  
  25. Csiszar A, Labinskyy N, Jo H, Ballabh P, Ungvari Z. Differential Pro-inflammatory and Pro-oxidant Effects of Bone Morphogenetic Protein-4 in Coronary and Pulmonary Arterial Endothelial Cells  Am J Physiol Heart Circ Physiol.  2008;295(2):H569-77
  26. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Couteur DL, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z,Sinclair DA, de Cabo R: Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span. Cell Metabolism 2008;8(2):157-68.
  27. Csiszar A, Wang M, Lakatta E, Ungvari Z: Inflammation and endothelial dysfunction during aging: role of NF-?B J Appl Physiol 2008 105(4):1333-41.
  28. Csiszar A, Labinskyy N, Podlutsky A, Kaminski PM, Wolin MS, Zhang C, Mukhopadhyay P, Pacher P, Hu F, de Cabo R, Ballabh P, Ungvari Z. Vasoprotective Effects of Resveratrol and SIRT1: Attenuation of Cigarette Smoke-induced Oxidative Stress and Pro-inflammatory Phenotypic Alterations. Am J Physiol 2008 ;294(6):H2721-35.
  29. Csiszar A, Ungvari Z: Endothelial Dysfunction and Vascular Inflammation in Type II Diabetes: Interaction of AGE/RAGE and TNFα Signaling. Am J Physiol 2008;295(2):H475
    27. Csiszar A, Labinskyy N, Perez V, Recchia FA, Podlutsky A, Mukhopadhyay P, Losonczy G, Pacher P, Austad SN, Bartke A, Ungvari Z. Endothelial function and vascular oxidative stress in long-lived GH/IGF-deficient Ames dwarf mice. Am J Physiol 2008;295(5):H1882-94.
  30. Csiszar A, Podlutsky A, Wolin MS, Losonczy G, Pacher P, Ungvari Z. Oxidative-nitrosative stress and accelerated vascular aging: implications for cigarette smoking. Frontiers Biosci 2009 (in press)
  31. Csiszar A, Lehoux S, Ungvari Z. Hemodynamic forces, vascular oxidative stress and regulation of BMP2/4 expression Antiox Redox Signal 2009 (in press)
  32. Addabbo F, Ratliff B, Park HC, Kuo M, Ungvari Z, Csiszar A, Krasnikov B, Sodhi K, Zhang F, Nasjletti A, Goligorsky MS.: Oxidative phosphorylation and mitochondrial mass are early victims of endothelial dysfunction: proteomic approach. Am J Pathol, 2009;174(1):34-43. 
  33. Rakhee S Gupte RS, Floyd BC, Kozicky M, George S, Ungvari Z, Neito V, Wolin MS, Gupte SA. Synergistic Activation of Glucose-6-Phosphate Dehydrogenase and NAD(P)H oxidase  by Src kinase Elevates Superoxide in Type 2 Diabetic, Zucker fa/fa, Rat Liver. Free Radical Biology & Medicine, 2009 ;47(3):219-28
  34. Zia MT, Csiszar A, Labinskyy N, Hu F, Vinukonda G, LaGamma EF, Ungvari Z, Ballabh P: Oxidative- Nitrosative Stress in a Rabbit Pup Model of Germinal Matrix hemorrhage: Role of NAD(P)H Oxidase, Stroke 2009; 40(6):2191-8.
  35. Labinskyy N, Mukhopadhyay P, Toth J, Szalai G, Veres M, Losonczy G, Pinto JT, Pacher P, Praveen B, Podlutsky A, Austad SN, Csiszar A, Ungvari Z. Longevity is associated with increased vascular resistance to high glucose-induced oxidative stress and inflammatory gene expression in P. leucopus. Am J Physiol 2009; 296(4):H946-56.  
  36. Zhang H, Zhang J, Ungvari Z, Zhang C. Resveratrol Improves Endothelial Function: Role of TNFα and Vascular Oxidative Stress. Arterioscler, Thromb, Vasc Biol 2009;29(8):1164-71.
  37. Csiszar A, Labinskyy N, Pinto JT, Ballabh P, Zhang H, Losonczy G, Pearson K, de Cabo R, Pacher P, Zhang C, Ungvari Z.: Resveratrol induces mitochondrial biogenesis in endothelial cells. Am J Physiol 2009; 297(1):H13-20.
  38. Chua C, Chahboune H, Braun A, Dummula K, Hu F, Chua CE, Yu J, Ungvari Z, Sherbany A, Hyder F, Ballabh P: Consequences of Intraventricular Hemorrhage in a Rabbit Pup Model Stroke 2009; 40(10):3369-77.
  39. Csiszar A, Labinskyy N, Xiangmin Z, Gupte SA, Wu JM, Losonczy G, de Cabo R Mathew R, Wolin MS, Ungvari Z: Resveratrol Prevents Monocrotaline-induced Pulmonary Hypertension in Rats Hypertension 2009; 54(3):668-75.
  40. Ungvari Z, Labinskyy N, Mukhopadhyay P, Pinto JT, Bagi Z, Ballabh P, Zhang C, Pacher P, Csiszar A. Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells Am J Physiol 2009 (in press)
  41. Csiszar A, Labinskyy N, Jimenez R, Pinto JT, Ballabh P, Losonczy G, Pearson KJ, de Cabo R, Ungvari Z. Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: role of circulating factors and SIRT1. Mech Ageing Dev. 2009 Aug;130(8):518-27.

ALL PUBLICATIONS: PubMed