Abstract
The last few decades have witnessed an increased life expectancy of patients suffering with systemic rheumatic diseases, mainly due to improved management, advanced therapies and preventative measures. However, autoimmune disorders are associated with significantly enhanced cardiovascular morbidity and mortality not fully explained by traditional cardiovascular disease (CVD) risk factors. It has been suggested that interactions between high-grade systemic inflammation and the vasculature lead to endothelial dysfunction and atherosclerosis, which may account for the excess risk for CVD events in this population. Diminished nitric oxide synthesis—due to down regulation of endothelial nitric oxide synthase—appears to play a prominent role in the imbalance between vasoactive factors, the consequent impairment of the endothelial hemostasis and the early development of atherosclerosis. Asymmetric dimethylarginine (ADMA) is one of the most potent endogenous inhibitors of the three isoforms of nitric oxide synthase and it is a newly discovered risk factor in the setting of diseases associated with endothelial dysfunction and adverse cardiovascular events. In the context of systemic inflammatory disorders there is increasing evidence that ADMA contributes to the vascular changes and to endothelial cell abnormalities, as several studies have revealed derangement of nitric oxide/ADMA pathway in different disease subsets. In this article we discuss the role of endothelial dysfunction in patients with rheumatic diseases, with a specific focus on the nitric oxide/ADMA system and we provide an overview on the literature pertaining to ADMA as a surrogate marker of subclinical vascular disease.
Highlights
Over the last years the importance of vascular disease in terms of cardiovascular morbidity and global mortality in patients with systemic rheumatic diseases has been extensively investigated and recognized
Endothelial cell abnormalities are common in asymptomatic individuals with cardiovascular disease (CVD) risk factors [16] and they convey prognostic significance regarding the occurrence of CVD events [17]
In patients with systemic autoimmune diseases, the prevention of CVD risk is regarded as part of the global management along with controlling of disease activity and inflammation
Summary
Over the last years the importance of vascular disease in terms of cardiovascular morbidity and global mortality in patients with systemic rheumatic diseases has been extensively investigated and recognized. Recent insights elucidating inflammation and autoimmunity as important contributing factors to the pathogenetic mechanisms of atherosclerosis, have stimulated renewed interest in the vascular damage and the associated CVD risk in patients with rheumatic diseases. Inflammation in this population has a systemic nature and it has been suggested that inflammatory molecules and cytokines originating from the inflamed synovium or the liver may have systemic vascular consequences resulting in endothelial dysfunction which is a pivotal early step in atherogenesis [11]. First the role of NO/ADMA pathway in the vascular and endothelium hemostasis is discussed
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