 |
Stanley L. Hazen, M.D., Ph.D.Staff
Dept. of Cell Biology |
Area of general research interest:
Mechanisms of atherosclerosis; leukocyte peroxidases; nitric oxide and reactive oxygen species; oxidant injury in asthma and other inflammatory diseases; cardiovascular genetics
Current program:
- Role of myeloperoxidase in oxidant stress and atherosclerosis
- Eosinophils and the origins of tissue injury in asthma
- Oxidative mechanisms and atherosclerotic plaque progression/regression
- Peroxidases and nitric oxide-related species
- Molecular determinants of vulnerable plaque
- Cardiovascular genetics
Investigators:
- Melanie Bodine, Senior Technologist
- Brennan, Marie-Luise, Ph.D., Research Scholar
- Kim Brinson, Technician
- Jaewoo Choi, Graduate Student
- Yoon-Mi Chung, Senior Technologist
- DiDonato, Joseph, Ph.D., Laboratory Director / Staff Scientist
- Xiao Ming fu, Lead Technologist
- Shengqiang Gao, Ph.D., Fellow
- Valentin Gogonea, PH.D., Adjunt Staff
- Greenberg, Michael, Ph.D., Research Associate
- Ying Huang, Ph.D., Fellow
- Elizabeth Klipfell, Ph.D., Senior Technologist
- Robert Koeth, Medical Student
- Xavier Lee, Ph.D., Research Scholar
- Bruce Levison, Ph.D., Project Staff
- Xin-Min Li, Ph.D., Research Associate
- Joseph Lupica, Graduate Student
- Shirley Mann, Senior Technologist
- Steve Maximuk, Technologist
- Darrell Rubin, Visiting Scientist
- David Schmitt, Lead Technologist
- Ephraim Sehayek, MD., Prokect Scientist
- Thomas Tallant, Ph.D., Fellow
- Xingwu Teng, Ph.D., Research Associate
- Arundhati Undurti, Graduate Student
- Frederick Van Lente, Ph.D., Consultant
- Zeneng Wang, Ph.D., Research Associate
- Raquel Williams, Technician
- Zhiping Wu, Ph.D., Research Associate
- Maryam Zamanian-Daryoush, Ph.D., Research Associate
- Renliang Zhang, Ph.D., Project Scientist
Collaborators:
- Ellis, Steve, M.D., Department of Cardiovascular Medicine, Cleveland Clinic Foundation
- Erzurum, Serpil M.D., Department of Cancer Biology, Cleveland Clinic Foundation
- Febbraio, Maria Ph.D., Department of Cell Biology, Cleveland Clinic Foundation
- Feldstein, Ariel, Ph.D., Departments of Pediatric Gastroenterology and Cell Biology, Cleveland Clinic Foundation
- Fox, Paul, Ph.D., Department of Cell Biology, Cleveland Clinic Foundation
- Gogonea, Valentin, Ph.D., Department of Chemistry, Cleveland State University
- Gornik, Heather, M.D., Department of Cardiovascular Medicine, Cleveland Clinic Foundation
- Ischiropoulos, Harry, Ph.D., Departments of Pediatrics, Biochemistry and Biophysics, University of Pennsylvania,
- McIntyre, Thomas, Ph.D., Department of Cell Biology, Cleveland Clinic Foundation
- Nicholls, Steve, M.D., Ph.D., Department of Cell Biology, Cleveland Clinic Foundation
- Nissen, Steve, M.D., Department of Cardiovascular Medicine, Cleveland Clinic Foundation
- Silverstein, Roy M.D., Department of Cell Biology, Cleveland Clinic Foundation
- Salomon, Robert, Ph.D., Chemistry Department, Case Western Reserve University, Cleveland
- Schauer, Phil, M.D., Department of Surgery, Cleveland Clinic Foundation
- Smith, Jonathan, Ph.D., Department of Cell Biology, Cleveland Clinic Foundation
- Stuehr, Dennis, Ph.D., Department of Immunology, Cleveland Clinic Foundation
- Tang, Wilson, Ph.D., Department of Cell Biology, Cleveland Clinic Foundation
- Topol, Eric, M.D., Department of Genetics, Case Western Reserve University
- Tuzcu, E. Murat, M.D., Department of Cardiovascular Medicine, Cleveland Clinic Foundation
- van Lente, Fred, Ph.D., Department of Clinical Pathology, Cleveland Clinic Foundation
Brief Description:
A long term goal of my laboratory is to understand the mechanisms through which inflammation and oxidative damage contributes to diseases such as atherosclerosis and asthma. A parallel objective is to investigate genetic and biochemical determinants cardiovascular disease. Several major research programs are currently under investigation. The first focuses on the role of myeloperoxidase, a heme protein present in neutrophils, monocytes and certain tissue macrophages, in promoting oxidant stress in vivo, and its potential participation in cardiovascular diseases. The second area focuses on HDL structure/function, and mechanisms for rendering HDL dysfunctional within human atheroma. The third area focuses on the role of eosinophils in mediating oxidative tissue injury in asthma. A fourth area of research interest is to identify the pathways responsible for development of vulnerable plaque and sudden cardiac death. Finally, a fifth area of investigation is to identify genetic determinants of cardiovascular disease initiation and propagation. All research projects rely on multidisciplinary approaches to identify specific oxidation pathways operational in innate immunity and inflammatory diseases. Research efforts in each program span from bench to bedside, including biochemical and biophysical studies on peroxidase catalytic mechanisms, genetic, cellular and animal model studies assessing biochemical and functional roles of specific oxidation pathways, and performance of human clinical studies aimed at elaborating the contributions of specific inflammatory pathways to disease pathogenesis.
References:
Recent Publications
Thomson L, Christie J, Vadseth C, Lanken PN, Fu X, Hazen SL, Ischiropoulos H. Identification of immunoglobulins that recognize 3-nitrotyrosine in patients with acute lung injury after major trauma. Amer. J. Resp. Cell Molec. Biol. (2007) 36:152-7.
Nicholls SJ, Tuzcu EM, Wolski K, Sipahi I, Schoenhagen P, Crowe T, Kapadia SR, Hazen SL, Nissen SE. Coronary artery calcification and changes in atheroma burden in response to established medical therapies. J Am Coll Cardiol. (2007) 49:263-70.
Blum S, Asaf R, Guetta J, Miller-Lotan R, Asleh R, Kremer R, Levy NS, Berger FG, Aronson D, Fu X, Zhang R, Hazen SL, Levy AP. Haptoglobin genotype determines myocardial infarct size in diabetic mice. J Am Coll Cardiol. (2007) 49:82-7.
Hsiai TK, Hwang J, Barr ML, Correa A, Hamilton R, Alavi M, Rouhanizadeh M, Cadenas E, Hazen SL. Hemodynamics influences vascular peroxynitrite formation: Implication for low-density lipoprotein apo-B-100 nitration. Free Radical Biol Med. (2007) 42:519-529.
Nicholls SJ, Tuzcu EM, Sipahi I, Grasso AW, Schoenhagen P, Hu T, Wolski K, Crowe T, Desai MY, Hazen SL, Kapadia SR, Nissen SE. Statins, high-density lipoprotein cholesterol, and regression of coronary atherosclerosis. JAMA. (2007)297:499-508.
Tardif JC, Gregoire J, L'allier PL, Ibrahim R, Anderson TJ, Reeves F, Title LM, Schampaert E, Lemay M, Lesperance J, Scott R, Guertin MC, Brennan ML, Hazen SL, Bertrand OF; for the CART-2 Investigators. Effects of the antioxidant succinobucol (AGI-1067) on human atherosclerosis in a randomized clinical trial. Atherosclerosis. (2007) 197(1): 480-6.
Li XM, Salomon RG, Qin J, Hazen SL. Conformation of endogenous ligand in membrane bilayer for the macrophage scavenger receptor CD36. Biochemistry (2007) 46(17):5009-17.
Nicholls SJ, Wolski K, Sipahi I, Schoenhagen P, Crowe T, Kapadia SR, Hazen SL, Tuzcu EM, Nissen SE. Rate of progression of coronary atherosclerotic plaque in women. J Am Coll Cardiol. (2007) 49(14):1546-51.
Nicholls SJ, Tuzcu EM, Hsu A, Wolski K, Sipahi I, Schoenhagen P, Crowe T, Kapadia SR, Hazen SL, Nissen SE. Comparison of coronary atherosclerotic volume in patients with glomerular filtration rates < or = 60 versus > 60 ml/min/1.73 m(2): a meta-analysis of intravascular ultrasound studies. Am J Cardiol. (2007) 99(6):813-6.
Meuwese MC, Stroes ESG, Hazen SL, van Miert JN, Kuivenhoven JA, Schaub RG, Wareham NJ, Luben R, Kastelein JJP, Khaw KT, Boekholdt SM. Serum Myeloperoxidase Levels Are Associated With the Future Risk of Coronary Artery Disease in Apparently Healthy Individuals: The EPIC-Norfolk Prospective Population Study. J Am Coll Cardiol. (2007) 50: 159-165.
Tang WHW, Tong W, Troughton RW, Martin MG, Shrestha K, Borowski A, Jasper S, Hazen SL, Klein AL, Prognostic value and echocardiographic determinants of plasma myeloperoxidase levels in chronic heart failure. J Am Coll Cardiol. (2007) 49:2364-2370.
Bhatt DL, Chew DP, Grines C, Mukherjee D, Leesar M, Gilchrist IC, Corbelli JC, Blankenship JC, Eres A, Steinhubl S, Tan WA, Resar JR, AlMahameed A, Abdel-Latif A, Tang HW, Brennan D, McErlean E, Hazen SL, Topol EJ. Peroxisome proliferator-activated receptor gamma agonists for the Prevention of Adverse events following percutaneous coronary Revascularization--results of the PPAR study. Am Heart J. (2007) 154:137-43.
Parastatidis I, Thomson L, Fries DM, Moore RE, Tohyama J, Fu X, Hazen SL, Heijnen HF, Dennehy MK, Liebler DC, Rader DJ, Ischiropoulos H. Increased protein nitration burden in the atherosclerotic lesions and plasma of apolipoprotein A-I-deficient mice. Circ Res. (2007) 101: 368-376.
Dzavik V, Cotter G, Reynolds HR, Alexander JH, Ramanathan K, Stebbins AL, Hathaway D, Farkouh ME, Ohman EM, Baran DA, Prondzinsky R, Panza JA, Cantor WJ, Vered Z, Buller CE, Kleiman NS, Webb JG, Holmes DR, Parrillo JE, Hazen SL, Gross SS, Harrington RA, Hochman JS. Effect of nitric oxide synthase inhibition on haemodynamics and outcome of patients with persistent cardiogenic shock complicating acute myocardial infarction: a phase II dose-ranging study. Eur Heart J. (2007) 28:1109-16.
McComsey GA, O'Riordan M, Hazen SL, El-Bejjani D, Bhatt S, Brennan ML, Storer N, Adell J, Nakamoto DA, Dogra V. Increased carotid intima media thickness and cardiac biomarkers in HIV infected children. AIDS. (2007) 21:921-7.
Lee JC, Weissglas-Volkov D, Kyttala M, Sinsheimer JS, Jokiaho A, de Bruin TW, Lusis AJ, Brennan ML, van Greevenbroek MM, van der Kallen CJ, Hazen SL, Pajukanta P. USF1 contributes to high serum lipid levels in Dutch FCHL families and U.S. whites with coronary artery disease. Arterioscler Thromb Vasc Biol. (2007) 50:159-65.
Wu Z, Wagner MA, Zheng L, Parks JS, Shy JM 3rd, Smith JD, Gogonea V, Hazen SL. The refined structure of nascent HDL reveals a key functional domain for particle maturation and dysfunction. Nat Struct Mol Biol. (2007) 14: 861-8.
Podrez EA, Byzova1 TV, Febbraio M, Salomon RG, Ma Y, Valiyaveettil M, Poliakov E, Sun M, Finton PJ, Curtis BR, Chen J, Zhang R, Silverstein RL, Hazen SL.Platelet CD36 links hyperlipidemia, oxidant stress and a pro-thrombotic phenotype. Nature Medicine (2007) 13:1086-1095.
Wang Z, Nicholls SJ, Rodriguez ER, Kummu O, Hörkkö S, Barnard J, Topol EJ, Hazen SL. Protein carbamylation as a mechanism linking inflammation, smoking, uremia and atherogenesis. Nature Medicine (2007) 13:1176-84.
Shen GQ, Li L, Girelli D, Seidelmann SB, Rao S, Fan C, Park JE, Xi Q, Li J, Hu Y, Olivieri O, Marchant K, Barnard J, Corrocher R, Elston R, Cassano J, Henderson S, Hazen SL, Plow EF, Topol EJ, Wang QK. An LRP8 variant is associated with familial and premature coronary artery disease and myocardial infarction. Am J Hum Genet. (2007) 81:780-91.
Cannady SB, Batra PS, Leahy R, Citardi MJ, Janocha A, Ricci K, Comhair SA, Bodine M, Wang Z, Hazen SL, Erzurum SC. Signal transduction and oxidative processes in sinonasal polyposis. J Allergy Clin Immunol. (2007) 120(6):1346-53.
Nicholls SJ, Wang Z, Koeth R, Levison B, DelFraino B, Dzavik V, Griffith OW, Hathaway D, Stasiv Y, Hochman JS, Panza JA, Nissen SE, Hazen SL. Metabolic profiling of arginine and nitric oxide pathways predicts hemodynamic abnormalities and mortality in patients with cardiogenic shock following acute myocardial infarction. Circulation (2007) 116(20):2315-24.
Greenberg ME, Li XM, Gugiu BG, Gu X, Qin J, Salomon RG, Hazen SL. The lipid whisker model of the structure of oxidized cell membranes. J. Biol. Chem. (2008) 283:2385-96.
Shen GQ, Rao S, Martinelli N, Li L, Olivieri O, Corrocher R, Abdullah KG, Hazen SL, Smith J, Barnard J, Plow EF, Girelli D, Wang QK. Association between four SNPs on chromosome 9p21 and myocardial infarction is replicated in an Italian population. J. Hum. Genet. (2008) 53(2):144-50.
Ioachimescu AG, Brennan DM, Hoar BM, Hazen SL, Hoogwerf BJ. Serum uric acid is an independent predictor of all-cause mortality in patients at high risk of cardiovascular disease: A preventive cardiology information system (PreCIS) database cohort study. Arthritis Rheum. (2008) 58(2):623-630.
Chen X, Zhang W, Laird J, Hazen SL, Salomon RG. Polyunsaturated phospholipids promote the oxidation and fragmentation of gamma-hydroxyalkenals: Formation and reactions of oxidatively truncated ether phospholipids. J. Lipid Res. (2008) 49(4): 832-46.
Morrow DA, Sabatine MS, Brennan ML, de Lemos JA, Murphy SA, Ruff CT, Rifai N, Cannon CP, Hazen SL. Concurrent evaluation of novel cardiac biomarkers in acute coronary syndrome: Myeloperoxidase, and soluble CD40 ligand and the risk of recurrent ischemic events in TACTICS-TIMI 18. Eur. Heart J. (2008) In Press.
Bhattacharyya T, Nicholls SJ, Topol EJ, Zhang R, Yang X, Schmitt D, Fu X, Shao M, Brennan DM, Ellis SG, Brennan M-L, Allayee H, Lusis AJ, Hazen SL. Relationship of paraoxonase (PON1) gene polymorphisms and functional activity with systemic oxidative stress and cardiovascular risk. J. Amer. Med. Assoc. (2008) 299(11): 1265-76.
Cho L, Hoogwerf B, Huang J, Brennan DM, Hazen SL. Gender Differences in Utilization of Effective Cardiovascular Secondary Prevention: A Cleveland Clinic Prevention Database Study. J Womens Health (Larchmt). (2008) In Press.