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Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Editorial Board Member: Gillery, Philippe / Kazmierczak, Steven / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Schlattmann, Peter / Whitfield, John B.

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Circulating levels of nitrated apolipoprotein A-I are increased in type 2 diabetic patients

Ricardo Hermo1 / Cristina Mier2 / Mary Mazzotta3 / Masatomi Tsuji4 / Satoshi Kimura5 / Alejandro Gugliucci6

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Corresponding author: Alejandro Gugliucci, MD, PhD, Research Director, Professor of Biochemistry, Touro University-California, Mare Island Building H-83, 1310, Johnson Lane, Vallejo, CA 94592, USA Phone: +1-707-6385237, Fax: +1-707-6385255,

Citation Information: Clinical Chemical Laboratory Medicine. Volume 43, Issue 6, Pages 601–606, ISSN (Online) 1437-4331, ISSN (Print) 1434-6621, DOI: 10.1515/CCLM.2005.104, July 2005

Publication History

Received:
January 25, 2005
Accepted:
April 14, 2005
Published Online:
2005-07-05

Abstract

Recent work has shown that high-density lipoprotein (HDL) isolated from human atherosclerotic lesions and the blood of patients with established coronary artery disease contains elevated levels of 3-nitrotyrosine and 3-chlorotyrosine. A higher nitrotyrosine content in lipoprotein is significantly associated with diminished cholesterol efflux capacity of the lipoprotein. Since accelerated atherogenesis is a key complication of diabetes mellitus, and nitrosative stress has recently been implicated in diabetic pathology, we set out to demonstrate an increase in the circulating levels of nitrated apolipoprotein A (apoA)-I in type 2 diabetic patients and its putative correlation with metabolic biomarkers. In this work we addressed this hypothesis in a case-control study with 30 type 2 diabetic patients and 30 age-matched control subjects. Nitrated apoA-I was 3280±1910 absorbance peak area/apoA-I (g/L) for diabetic patients and 2320±890 for control subjects (p<0.037). This represents a 50% increase in circulating nitrated apoA-I in diabetic patients to age-matched controls. Diabetic patients also showed increases of a similar magnitude in circulating advanced glycation endproducts measured as pentosidine fluorescence (44.16±16.26 vs. 30.84±12.86 AU; p<0.01) and in circulating lipoperoxides (46.0±18.0 vs. 37.2±18.0 nmol/L; p<0.03). No significant correlation was found between nitration of apoA-I and glycosylated hemoglobin or any of the other parameters measured. If proven in subsequent functional and in vivo studies, increased nitrated apoA-I would represent another mechanism by which nitrosative stress participates in diabetic macro-angiopathy.

Keywords: diabetes; high-density lipoprotein (HDL); macroangiopathy, myeloperoxidase; nitrosative stress; peroxynitrite.

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