Do cardiac risk factors affect the homocysteine and asymmetric dimethylarginine relationship in patients with coronary artery diseases?

Department of Biochemistry, Ege University, Faculty of Medicine, Izmir, Turkey.
Clinical biochemistry (Impact Factor: 2.02). 06/2012; 45(16-17). DOI: 10.1016/j.clinbiochem.2012.06.024
Source: PubMed

ABSTRACT OBJECTIVES: Elevated homocysteine (Hcy) concentrations have been shown to be a risk factor for atherosclerotic vascular disease and thrombosis. Increased asymmetric dimethylarginine (ADMA) levels have been implicated in the pathogenesis of numerous conditions affecting the cardiovascular system. In this study, the influence of cardiovascular risk factors and other variables on Hcy and ADMA relationship in patients with coronary artery disease (CAD) was investigated. DESIGN AND METHODS: Seventy-five patients with CAD were divided into three tertiles according to their Hcy levels. The effect of age, gender, blood pressure, lipid profile, renal function, and the presence of diabetes, insulin resistance, heart failure, inflammation, overweight, smoking and severity of coronary atherosclerosis on Hcy and ADMA relationship was evaluated. RESULTS: ADMA concentrations of patients in the middle and highest Hcy tertiles were significantly higher than the patients in the lowest tertile. When ADMA concentrations were adjusted for demographic, clinical and laboratory variables, the significant differences in ADMA concentrations between the tertiles were preserved. ADMA levels positively correlated with Hcy. Homocysteine levels positively correlated with serum creatinine and NT-proBNP concentrations and negatively correlated with glomerular filtration rates. Stepwise multiple regression analysis revealed Hcy as the unique predictor of ADMA levels. CONCLUSION: Homocysteine concentration has an effect on ADMA levels. There is a strong correlation between Hcy and ADMA. Cardiovascular risk factors do not have an influence on this relationship.

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    ABSTRACT: Diabetic nephropathy (DN) is a major cause of end-stage kidney disease, and therefore early diagnosis and intervention may help reverse renal damage. One hundred and sixty-eight patients with T2DM and 56 healthy volunteers (control group) were enrolled at Shandong University Qilu Hospital between April 2010 and October 2012. All subjects underwent blood sampling for sera homocysteine (Hcy) and cystatin C (Cys C) assays and a urine microalbumin test. The patients were divided into three groups according to the urine microalbumin excretion rate (UMAER): the simple DM group (SDM group, n = 51), the early-stage DN group (EDN group, n = 60), and the clinical DN and renal failure group (CDN group, n = 57). Correlation analysis was performed to examine the association between sera Hcy and Cys C levels with UMAER. Our findings showed that sera Hcy level, Cys C level, and UMAER increased significantly in the SDM group (P < 0.05, P < 0.01), the EDN group (P < 0.01), and the CDN group (P < 0.01) as compared with the control group. These three biochemical markers also increased significantly with DN progression (P < 0.01). Correlation analysis showed that sera Hcy and Cys C levels were positively correlated with UMAER (r = 0.702, P < 0.01; r = 0.873, P < 0.01). In conclusion, our results showed that sera Hcy and Cys C levels increased consistently with the development and progression of DN as indicated by UMAER. Sera Hcy and Cys C are sensitive biomarkers for the detection of early-stage DN and monitoring its progression.
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    ABSTRACT: Homocystinuria is a neurometabolic disease caused by a severe deficiency of cystathionine beta-synthase activity, resulting in severe hyperhomocysteinemia. Affected patients present several symptoms including a variable degree of motor dysfunction. In this study, we investigated the effect of chronic hyperhomocysteinemia on the cell viability of the mitochondrion, as well as on some parameters of energy metabolism, such as glucose oxidation and activities of pyruvate kinase, citrate synthase, isocitrate dehydrogenase, malate dehydrogenase, respiratory chain complexes and creatine kinase in gastrocnemius rat skeletal muscle. We also evaluated the effect of creatine on biochemical alterations elicited by hyperhomocysteinemia. Wistar rats received daily subcutaneous injections of homocysteine (0.3-0.6 µmol/g body weight) and/or creatine (50 mg/kg body weight) from the 6th to the 28th days of age. The animals were decapitated 12 h after the last injection. Homocysteine decreased the cell viability of the mitochondrion and the activities of pyruvate kinase and creatine kinase. Succinate dehydrogenase was increased other evaluated parameters were not changed by this amino acid. Creatine, when combined with homocysteine, prevented or caused a synergistic effect on some changes provoked by this amino acid. Creatine per se or creatine plus homocysteine altered glucose oxidation. These findings provide insights into the mechanisms by which homocysteine exerts its effects on skeletal muscle function, more studies are needed to elucidate them. Although creatine prevents some alterations caused by homocysteine, it should be used with caution, mainly in healthy individuals because it could change the homeostasis of normal physiological functions. Copyright © 2012 John Wiley & Sons, Ltd.
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