Accessible Requires Authentication Published by De Gruyter July 5, 2005

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

Ricardo Hermo, Cristina Mier, Mary Mazzotta, Masatomi Tsuji, Satoshi Kimura and Alejandro Gugliucci

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±18.0nmol/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.


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,

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Received: 2005-1-25
Accepted: 2005-4-14
Published Online: 2005-7-5
Published in Print: 2005-6-1

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