Anna Csiszár MD, PhD

 

Associate Professor, Donald W. Reynolds Chair of Aging Research

Contact

University of Oklahoma Health Sciences Center
975 NE 10th Street   BRC 1315
Oklahoma City, OK 73104
Telephone: (405) 271-8000 (ext 47830)
Email: anna-csiszar@ouhsc.edu

Education

M.D., 1998  Semmelweis University, Budapest, Hungary
Ph.D., 2003 Semmelweis University, Budapest, Hungary
American Heart Association Post-doctoral fellowship, New York Medical College, Valhalla, NY

Research Interests

  • Cardiovascular Pathophysiology
  • Molecular Biology of Aging
  • Cell Biology

Research in Dr. Csiszár's laboratory is focused on the role of oxidative stress and inflammation in development of cardiovascular diseases in aging and metabolic diseases

Active areas of research include:

  1. Cerebrovascular protective effects of the GH/IGF-1 system in aging: 
    There is increasing evidence that age-related dysfunction of the GH/IGF-1 system is a risk factor for the development of cardiovascular diseases in the elderly. Our recent results obtained in hypopituitary Ames dwarf mice support the view that the GH/IGF-1 axis exerts primarily vasoprotective functions by up-regulating vascular antioxidant defenses, whereas lack of GH/IGF-1 elicits endothelial oxidative stress adversely affecting NO bioavailability and endothelium-dependent vasorelaxation. Because plasma GH and IGF1 levels decline with age in healthy humans and in experimental animals, it is possible that GH/IGF-1 deficiency may contribute to age-related endothelial oxidative stress and vasodilator dysfunction promoting the development of vascular disease. Our ongoing studies aim to test the hypothesis that 1) decreases in IGF-1 levels in the cerebral microcirculation enhances mitochondrial oxidative stress and NF-?B activation, resulting in a pro-inflammatory cytokine microenvironment and leukocyte extravasation promoting neuroinflammation in aging and that 2) treatment with growth hormone/IGF-1 protects the cerebrovasculature from the deleterious effects of oxidative stress and inflammation associated with aging. We posit that anti-oxidative and anti-inflammatory effects of IGF-1 contribute significantly to an intervention strategy for neuroprotection and improvement of cognitive function during aging.
  2. Vasoprotection by Nrf2 activation:
    The literature is replete with evidence showing that oxidative stress plays a key role in the pro-atherogenic alterations of blood vessels both in aging and in metabolic diseases. Our goal is to identify novel mechanisms that act as regulators of vascular redox homeostasis and thus suppress oxidative stress-induced inflammatory processes in these pathophysiological conditions. NF-E2-related factor 2 (Nrf2) is a transcription factor activated by oxidative stress, which regulates the expression of numerous ROS detoxifying and antioxidant genes in liver and other organs. Nrf2-dependent pathways are expressed and functional in endothelial cells in culture. Our ongoing studies in mice fed a high fat diet demonsrtae that Nrf2 protects the cardiovascular system from oxidative stress in type 2 diabetes. 
  3. Mitochondrial dysfunction in vascular aging:
    There is a growing body of evidence that mitochondrial oxidative stress contributes to endothelial activation and vascular pro-atherogenic alterations in aging and in pathophysiological conditions associated with accelerated vascular aging (e.g. diabetes). Importantly, our recent studies have shown that aging increases mitochondrial H2O2 production in the endothelial cells of rat arteries, which contributes to NF-κB induction and endothelial activation in aged vessels. Our ongoing investigations focus on the emerging role of mitochondria in endothelial pathophysiological alterations in aging and the relationship between mitochondrial biogenesis and mitochondrial ROS production. We are testing the hypotheses that i) impaired NO bioavailability leads to dysregulation of mitochondrial biogenesis in aged arteries, and that ii)  activation of SIRT-1 in the vascular endothelial and smooth muscle cells induces mitochondrial biogenesis and attenuates mtROS production, which may attenuate vascular impairment in aging.

Dr. Csiszár's research has been continously funded by the American Heart Association and the American Federation for Aging Research. She has published more than 68 original manuscripts and invited reviews and has been invited to present his research at national and international meetings.

Recent Publications

  1. Ballabh P, Xu H, Hu F, Braun A, Smith K, Rivera A, Lou N, Ungvari Z, Goldman SA,Csiszar A, Nedergaard M. Angiogenic inhibition reduces germinal matrix hemorrhage. Nat Med. 2007;13(4):477-85.
  2. 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(2):H909-18.
  3. 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;27(44):12012-24.
  4. Csiszar A, Labinskyy N, Orosz Z, Xiangmin Z, Buffenstein R, Ungvari Z. Vascular aging in the longest-living rodent, the naked mole rat. Am J Physiol Heart Circ Physiol. 2007;293(2):H919-27.
  5. Csiszar A, Labinskyy N, Smith K, Rivera A, Orosz Z, Ungvari Z. Vasculoprotective effects of anti-tumor necrosis factor-alpha treatment in aging. Am J Pathol. 2007;170(1):388-98. PMCID: 1762698.
  6. Csiszar A, Labinskyy N, Smith KE, Rivera A, Bakker EN, Jo H, Gardner J, Orosz Z, Ungvari Z. Downregulation of bone morphogenetic protein 4 expression in coronary arterial endothelial cells: role of shear stress and the cAMP/protein kinase A pathway. Arterioscler Thromb Vasc Biol. 2007;27(4):776-82.
  7. Csiszar A, Labinskyy N, Zhao X, Hu F, Serpillon S, Huang Z, Ballabh P, Levy RJ, Hintze TH, Wolin MS, Austad SN, Podlutsky A, Ungvari Z. Vascular superoxide and hydrogen peroxide production and oxidative stress resistance in two closely related rodent species with disparate longevity. Aging Cell. 2007;6(6):783-97.
  8. Csiszar A, Toth J, Peti-Peterdi J, Ungvari Z. The aging kidney: role of endothelial oxidative stress and inflammation. Acta Physiol Hung. 2007;94(1-2):107-15.
  9. Orosz Z, Csiszar A, Labinskyy N, Smith K, Kaminski PM, Ferdinandy P, Wolin MS, Rivera A, Ungvari Z. Cigarette smoke-induced proinflammatory alterations in the endothelial phenotype: role of NAD(P)H oxidase activation. Am J Physiol Heart Circ Physiol. 2007;292(1):H130-9.
  10. Rajesh M, Mukhopadhyay P, Batkai S, Hasko G, Liaudet L, Huffman JW, Csiszar A, Ungvari Z, Mackie K, Chatterjee S, Pacher P. CB2-receptor stimulation attenuates TNF-alpha-induced human endothelial cell activation, transendothelial migration of monocytes, and monocyte-endothelial adhesion. Am J Physiol Heart Circ Physiol. 2007;293(4):H2210-8.
  11. Stef G, Csiszar A, Ziangmin Z, Ferdinandy P, Ungvari Z, Veress G. Inhibition of NAD(P)H oxidase attenuates aggregation of platelets from high-risk cardiac patients with aspirin resistance. Pharmacol Rep. 2007;59(4):428-36.
  12. Ungvari Z, Orosz Z, Labinskyy N, Rivera A, Xiangmin Z, Smith K, Csiszar A. Increased mitochondrial H2O2 production promotes endothelial NF-kappaB activation in aged rat arteries. Am J Physiol Heart Circ Physiol. 2007;293(1):H37-47.
  13. Ungvari Z, Orosz Z, Rivera A, Labinskyy N, Xiangmin Z, Olson S, Podlutsky A, Csiszar A. Resveratrol increases vascular oxidative stress resistance. Am J Physiol Heart Circ Physiol. 2007;292(5):H2417-24.
  14. Csiszar A, Labinskyy N, Jo H, Ballabh P, Ungvari Z. Differential proinflammatory and prooxidant effects of bone morphogenetic protein-4 in coronary and pulmonary arterial endothelial cells. Am J Physiol Heart Circ Physiol. 2008;295(2):H569-77.
  15. 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 Heart Circ Physiol. 2008;295(5):H1882-94.
  16. 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 proinflammatory phenotypic alterations. Am J Physiol Heart Circ Physiol. 2008;294(6):H2721-35.
  17. Csiszar A, Ungvari Z. Endothelial dysfunction and vascular inflammation in type 2 diabetes: interaction of AGE/RAGE and TNF-alpha signaling. Am J Physiol Heart Circ Physiol. 2008;295(2):H475-6.
  18. Csiszar A, Wang M, Lakatta EG, Ungvari ZI. Inflammation and endothelial dysfunction during aging: role of NF-{kappa}B. J Appl Physiol. 2008.
  19. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D Elliott PJ, 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 Metab. 2008;8(2):157-68.
  20. 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. Proc Natl Acad Sci U S A. 2008;105(7):2325-30.
  21. Ungvari Z, Buffenstein R, Austad SN, Podlutsky A, Kaley G, Csiszar A. Oxidative stress in vascular senescence: lessons from successfully aging species. Front Biosci. 2008;13:5056-70.
  22. Ungvari Z, Labinskyy N, Gupte S, 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.
  23. Ungvari Z, Parrado-Fernandez C, Csiszar A, de Cabo R. Mechanisms underlying caloric restriction and lifespan regulation: implications for vascular aging. Circ Res. 2008;102(5):519-28. PMCID: 2424221.
  24. Xu H, Hu F, Sado Y, Ninomiya Y, Borza DB, Ungvari Z, Lagamma EF, 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. 
  25. Adabbo F, Ratliff B, Park HC, Kuo M, Ungvari Z, Csiszar A, Krasnikof 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:in press.
  26. Labinskyy N, Mukhopadhyay P, Toth J, Szalai G, Veres M, Losonczy G, Pinto JT, Pacher P, Ballabh P, Podlutsky A, Austad SN, Csiszar A, Ungvari ZI. Longevity is associated with increased vascular resistance to high glucose-induced oxidative stress and inflammatory gene expression in P. leucopus. Am J Physiol Heart Circ Physiol. 2009.
  27. 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;130(8):518-27.
  28. Csiszar A, Labinskyy N, Olson S, Pinto JT, Gupte S, Wu JM, Hu F, Ballabh P, Podlutsky A, 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.
  29. 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 Heart Circ Physiol. 2009;297(1):H13-20.
  30. Csiszar A, Lehoux S, Ungvari Z. Hemodynamic forces, vascular oxidative stress and regulation of BMP-2/4 expression. Antioxid Redox Signal. 2009.
  31. Csiszar A, Podlutsky A, Wolin MS, Losonczy G, Pacher P, Ungvari Z. Oxidative stress and accelerated vascular aging: implications for cigarette smoking. Front Biosci. 2009;14:3128-44.
  32. Labinskyy N, Mukhopadhyay P, Toth J, Szalai G, Veres M, Losonczy G, Pinto JT, Pacher P, Ballabh P, 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 Peromyscus leucopus. Am J Physiol Heart Circ Physiol. 2009;296(4):H946-56.
  33. Ungvari ZI, 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 Heart Circ Physiol. 2009.
  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.

ALL PUBLICATIONS: PubMed