Circulating levels of nitrated apolipoprotein A-I are increased in type 2 diabetic patients.
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.
Hermo
Ricardo
R
Department of Clinical Laboratory, Facultad de Medicina, Universidad de la Republica, Montevideo, Uruguay.
Mier
Cristina
C
Mazzotta
Mary
M
Tsuji
Masatomi
M
Kimura
Satoshi
S
Gugliucci
Alejandro
A
D000368:Aged; D016632:Apolipoprotein A-I / Q000097:blood* / Q000378:metabolism; D001161:Arteriosclerosis / Q000209:etiology / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D048909:Diabetes Complications / Q000209:etiology / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000209:etiology / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood / Q000378:metabolism
D016632:Apolipoprotein A-I; D015415:Biomarkers; D006442:Glycated Hemoglobin; D009566:Nitrates