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: 7.76). 06/2010; 62(6):1718-22. DOI: 10.1002/art.27392
Source: PubMed


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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Available from: Jane E Salmon, Jul 03, 2015
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    • "This observation suggests that methionine-or hCys-induced endothelial dysfunction may not be due to ADMA or due to disruption of the methylation status. Thus far, there is only a single study reporting on a weak correlation (r = 0.229, P = 0.012) between circulating ADMA and hCys in systemic lupus erythematosus (Perna et al. 2010), a rheumatic disease. "
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    ABSTRACT: Elevated circulating concentrations of total L-homocysteine (thCys) and free asymmetric dimethylarginine (ADMA) are long-established cardiovascular risk factors. Low circulating L-homoarginine (hArg) concentrations were recently found to be associated with increased cardiovascular morbidity and mortality. The biochemical pathways of these amino acids overlap and share the same cofactor S-adenosylmethionine (SAM). In the present study, we investigated potential associations between hArg, L-arginine (Arg), ADMA and thCys in plasma of patients suffering from rheumatoid arthritis (RA), coronary artery disease (CAD) or peripheral artery occlusive disease (PAOD). In RA, we did not find any correlation between ADMA or hArg and thCys at baseline (n = 100) and after (n = 83) combined add-on supplementation of omega-3 fatty acids, vitamin E, vitamin A, copper, and selenium, or placebo (soy oil). ADMA correlated with Arg at baseline (r = 0.446, P < 0.001) and after treatment (r = 0.246, P = 0.03). hArg did not correlate with ADMA, but correlated with Arg before (r = 0.240, P = 0.02) and after treatment (r = 0.233, P = 0.03). These results suggest that hArg, ADMA and Arg are biochemically familiar with each other, but unrelated to hCys in RA. In PAOD and CAD, ADMA and thCys did not correlate.
    Amino Acids 01/2015; 47(9). DOI:10.1007/s00726-015-1915-3 · 3.29 Impact Factor
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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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    ABSTRACT: Oxidative stress reflects an imbalance between antioxidants and pro-oxidants. Many diseases like atherosclerosis or heart failure are involved in oxidative stress. Increased oxidative stress is one of the potential contributing factors to aging. The aim of this study was to monitor the total thiol levels as markers of oxidative stress in 20 healthy volunteers after polyphenols intake (extract from the French oak wood Quercus robur - Robuvit® (300 mg/day)). Polyphenols are known as biomodulators with antioxidant activities. Homocysteine, cysteine and glutathione total levels were determined by using HPLC with electrochemical detection. The activity of the antioxidant enzyme paraoxonase-1 toward two substrates was determined by spectrophotometry. The level of thiol compounds and paraoxonase-1 activities were controlled after run-in (week 0), intervention (week 4) and washout (week 6) period. After the intervention period the results showed that Robuvit® had no significant influence on glutathione level (p = 0.382) and paraoxonase activities towards both, arylester and lactone substrates. On the other hand, homocysteine and cysteine levels decreased significantly (p = 0.029; p < 0.001, respectively). The negative correlation between paraoxonase lactonase activity and homocysteine level was noticed. This confirms that paraoxonase might play an important role in homocysteine-thiolactone metabolism.
    General Physiology and Biophysics 11/2014; DOI:10.4149/gpb_2014029 · 1.17 Impact Factor
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    • "Kiani et al. [97] reported a significant correlation between coronary calcium—a marker of early atherosclerosis—and ADMA in systemic lupus erythematosus patients. In the same disease setting, ADMA has also been associated with arterial stiffness [98] and CVD events including coronary artery disease, ischemic cerebrovascular events and peripheral artery disease [99]. "
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    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.
    International Journal of Molecular Sciences 12/2012; 13(10):12315-35. DOI:10.3390/ijms131012315 · 2.86 Impact Factor
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