Article

Relationship of Asymmetric Dimethylarginine and Homocysteine to Vascular Aging in Systemic Lupus Erythematosus Patients

Weill Cornell Medical College and Hospital for Special Surgery, New York, New York 10021, USA.
Arthritis & Rheumatology (Impact Factor: 7.87). 06/2010; 62(6):1718-22. DOI: 10.1002/art.27392
Source: PubMed

ABSTRACT Systemic lupus erythematosus (SLE) is independently associated with accelerated atherosclerosis and premature arterial stiffening. Asymmetric dimethylarginine (ADMA) and homocysteine are mechanistically interrelated mediators of endothelial dysfunction and correlates of atherosclerosis in the general population. The aim of this study was to assess the relationship of ADMA and homocysteine to subclinical vascular disease in patients with SLE.
One hundred twenty-five patients with SLE who were participating in a study of cardiovascular disease underwent clinical and laboratory assessment, carotid artery ultrasonography to detect atherosclerosis, and radial artery applanation tonometry to measure arterial stiffness.
Neither ADMA nor homocysteine correlated with the presence or extent of carotid atherosclerosis. In contrast, ADMA was significantly related to the arterial stiffness index. Independent correlates of arterial stiffening included the ADMA concentration, the presence of diabetes mellitus, older age at the time of diagnosis, longer disease duration, and the absence of anti-Sm or anti-RNP antibodies. A secondary multivariable analysis substituting homocysteine for ADMA demonstrated comparable relationships with arterial stiffness (r(2) = 0.616 for homocysteine and r(2) = 0.595 for ADMA).
ADMA and homocysteine are biomarkers for and may be mediators of premature arterial stiffening in patients with SLE. Because arterial stiffness has independent prognostic value for cardiovascular morbidity and mortality, its predictors may identify patients who are at increased risk of cardiovascular disease.

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    • "HCy can inhibit the enzyme that metabolizes ADMA. It also increases synthesis of ADMA by activating the endoplasmic reticulum stress pathway (Perna et al. 2010). Both HCy and ADMA are thought to mediate their adverse vascular effects (van Guldener et al. 2007) and we assume that decrease HCy level has positive influence also on ADMA level (not shown). "
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