Cardiovascular Complications in Renal Diseases

Patients with chronic renal disease (CRD) represent an important segment of Tunisian population, and mostly because of the high risk of cardiovascular disease (CVD) associated with renal insufficiency, detection and treatment of chronic renal disease is now a public health priority (Abderrahim E et al., 2001, Ben Maïz H et al., 2006, Counil E et al., 2008). The increased incidence of CVD is likely to be the result of a high prevalence of both traditional risk factors, such as diabetes mellitus, hypertension, dyslipidemia and smoking. Non traditional risk factors, such as hyperhomocysteinemia, oxidative stress and inflammation have been taken into account. Homocysteine (Hcy) is an amino acid that circulates in the blood. An elevated serum concentration of homocysteine is a known risk factor for atherosclerosis and is associated with an increased risk of myocardial infraction and health. Accumulating evidence suggests that the Hcy thioester metabolite, hcy-thiolactone, has an important role in atherothrombosis. Hcy-thiolactone is a product of an error-editing reaction in protein biosynthesis, which forms when Hcy is mistakenly selected by methionyl-tRNA synthetase. The thioester chemistry of Hcy-thiolactone underlies its ability of form isopeptide bonds with protein lysines residues, which impairs or alters protein function. Protein targets for modification by Hcy-thiolactone include fibrogen, LDL, HDL, albumin, heamoglobin and ferritin. Pathophysiclogical consequences of protein N-homocyteinylation include protein and cell damage, activation of an adaptive immune response, synthesis of auto-antibodies against N-hcy-proteins, and enhanced thrombosis caused by N-hcy-fibrogen. The development of highly sensitive chemical and immunohistochemical assays has provided evidence for the contribution of the Hcy-thiolactone pathway to pathophysiology of the vascular system. In particular, conditions predisposing to atherosclerosis, such as genetic or dietary hyperhomocysteinemia, have been shown to lead to elevation of Hcy-thiolactone and N-hcy-protein. Oxidative stress plays an important role in the pathogenesis of atherosclerosis and cardiovascular disease. Reactive oxygen species (ROS) production is toxic via their effects on cellular components such as denaturing proteins, membrane lipids and DNA. Oxidative