Myeloperoxidase and paraoxonase-1 in type 2 diabetic patients |
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| Institution: | 1. Department of Internal Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;2. Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA;3. Data Analytics Center, University of Pennsylvania Health System, Philadelphia, PA;1. Penn Image-Guided Interventions Laboratory, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104;2. Department of Radiology, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104;3. Department of Pathology and Laboratory Medicine, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce St., Philadelphia, PA 19104;1. Cardiovascular Nutrition Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111, USA;2. Boston Heart Diagnostics, Framingham, MA 01702, USA;3. Metabolic Research Center, School of Medicine & Pharmacology and Faculty of Engineering, Computing and Mathematics, University of Western Australia, Perth, Australia;4. Department of Medicine, Division of Translational Medicine and Human Genetics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;5. Department of Medicine, Institute for Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA;1. Department of Epidemiology and Health Services Evaluation, The S. Daniel International Center for Health and Disease, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel;2. Metabolic Bone Disease Unit, Rambam Health Care Campus, Haifa, Israel;3. Center of Preventive Medicine, Rambam Health Care Campus, Haifa, Israel;4. Ruth and Bruce Rappaport Faculty of Medicine, Technion–Israel Institute of Technology, Israel;1. Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA;2. Center for Clinical and Epidemiologic Research, University of São Paulo, Brazil;3. Lipid Clinic Heart Institute (InCor), University of São Paulo Medical School Hospital, São Paulo, Brazil;4. Department of Clinical Family and Community Medicine, CGH Medical Center, Sterling, IL, USA;5. Postgraduate Studies Program in Epidemiology and Hospital de Clínicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil;1. Department of Medicine, Division of Hematology and Oncology, University of California, Los Angeles, CA 90095, USA;2. Department of Microbiology, Immunology, and Molecular Genetics, University of California, Los Angeles, CA 90095, USA |
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| Abstract: | Background and aimsReduced high density lipoproteins (HDL) and increased oxidative stress are features of type 2 diabetes. Myeloperoxidase is an oxidative enzyme partly associated with HDL and causing HDL dysfunction. It is an independent risk factor for cardiovascular disease. Paraoxonase-1 is an HDL-associated enzyme that protects against cardiovascular disease and is reduced in diabetes. The present study examined if serum myeloperoxidase was (i) increased in type 2 diabetes, (ii) correlated with paraoxonase-1 activity.Methods and resultsThe study was based on cross-sectional analyses of serum myeloperoxidase and paraoxonase-1 in type 2 diabetic patients and non-diabetic participants, with and without cardiovascular disease.Serum myeloperoxidase concentrations were not increased in type 2 diabetic patients without cardiovascular disease compared to non-diabetic controls. They were significantly higher in type 2 patients and non-diabetic patients with angiographically confirmed coronary disease. HDL-associated myeloperoxidase was correlated with serum myeloperoxidase (r = 0.80, p < 0.001) but not HDL-cholesterol (r = 0.08) or apolipoprotein AI (r = 0.08). Multivariate analyses showed serum myeloperoxidase to be an independent determinant of paraoxonase activities (arylesterase, p = 0.024; paraoxonase, p = 0.026).ConclusionsMyeloperoxidase is an independent, negative determinant of paraoxonase-1 activity, which may be one mechanism by which it promotes HDL dysfunction and increases cardiovascular risk. Increased serum myeloperoxidase is not a feature of type 2 diabetes in the absence of overt cardiovascular disease. The level of HDL-associated myeloperoxidase is determined by the serum concentration of the enzyme suggesting that, in the context of reduced HDL concentrations in diabetic patients, myeloperoxidase may have a greater impact on HDL function. |
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