Asymmetric Dimethyl Arginine (ADMA), Homocysteine and Semicarbazide-Sensitive Amine Oxidase Activity (SSAO): New Markers of Oxidative Stress in Acute Coronary Syndromes

Abstract number: P0496

Marcucci¹ R, Raimondi² L, Sofi¹ F, Rogolino¹ A, Lucarini¹ L, Casini³ A, Mugelli² A, Surrenti³ C, Abbate¹ R, Gensini¹ GF

¹¹Department of Medical and Surgical Critical Area, Thrombosis Centre, University of Florence, Italy; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy ¹¹Department of Medical and Surgical Critical Area, Thrombosis Centre, University of Florence, Italy; Azienda Ospedaliero-Universitaria Careggi, Florence, Italy ²²Department of Pharmacology, University of Florence, Italy ³³Department of Clinical Pathophysiology, Unit of Nutrition, University of Florence, Italy

High levels of Homocysteine (Hcy) are a well-established risk factor for atherosclerotic disease. One of the mechanism evoked to support its pathogenetic role in atherosclerosis is the induction of an oxidative stress. Ex-vivo reports documented an inhibitory effect of high levels of Hcy on the enzyme dymethyl arginine dymethylaminohydrolysis (DDAH) which converts the Asymmetric dimethyl arginine (ADMA) in citrullin. Elevated levels of ADMA, the most potent endogenous inhibitor of the nitric oxide synthase activity, are markers of endothelial dysfunction and are found elevated in patients with atherosclerosis. The semicarbazide-sensitive amine oxidase (SSAO) is a tissue-bound amine oxidase activity with adhesion properties highly expressed in the vasculature. For unknown reasons in the metabolic syndrome and in cardiovascular diseases, elevated levels are found but their pathological significance remains to establish. One hypothesis is that this enzymatic activity participate in generating endothelial dysfunction through the production of cytotoxic aldehydes and hydrogen peroxide. The aim of this study was to evaluate Hcy, ADMA levels and SSAO activity in patients with acute coronary syndromes (ACS). 75 patients (age 62.6 ± 11.6; 70 M/5 F) with ACS (51 AMI, 24 UA) referred to the Cardiologic Unit of the University of Florence and 75 controls (age 61 ± 9.8; 69 M/6 F) were enrolled. SSAO activity, ADMA and Hcy levels were significantly higher in patients than in controls (31.6 ± 4.6 pmol/mg/h vs 0–2 pmol/mg/h; 1851.58 ± 254.65 pmol/ml vs 520 ± 360 pmol/ml and 22.7 ± 18.4 micromol/l vs 12.3 ± 10.5 micromol/l). SSAO activity significantly correlated with Hcy (r = 0.57; P= 0.001) and Hcy levels significantly correlated with ADMA (r= 0.49; P < 0.005). In addition, ADMA positively correlated with the extension of necrosis in AMI patients (r= 0.46; P < 0.05). This is the first in-vivo demonstration that Hcy significantly correlates with ADMA levels in ACS. Furthermore, we found another possible factor which might play a role in the oxidative stress generated by hyperhomocysteinemia.