Serum Asymmetric Dimethylarginine Levels in Patients with Acute Rheumatic Fever: Inflammation and Endothelial Dysfunction

Endothelial dysfunction is considered to be an important and early step in the initiation and progression of atherosclerosis.[1] Nitric oxide is produced by the metabolism of l-arginine via endothelial NO synthase (eNOS) to maintain appropriate endothelial function (i.e., intracellular messaging, anti-inflammatory, antithrombotic, and antiapoptotic effects).[1] Serum asymmetric dimethylarginine (ADMA) is an endogenous analog of l-arginine.[2] Studies have found an association between elevated ADMA levels and endothelial dysfunction in humans, which may partly be related to eNOS uncoupling that results in increased eNOS-derived superoxide production in human vessels.[2] Serum ADMA levels have been associated with coronary atherosclerosis in patients with clinical risk factors as well as in healthy individuals.[3] [4] [5] Plasma levels of ADMA have been associated with mortality and a worsened clinical outcome in diabetic patients with established coronary atherosclerotic disease.[6]

The relationship between serum ADMA levels and acute rheumatic fever (ARF) is not well defined. ARF is a clinical state of heightened inflammation driven by an autoimmune reaction. Sert and collogues in the accompanying article “Serum Asymmetric Dimethylarginine Levels in Patients with Acute Rheumatic Fever” have reported the results of their case control study exploring the relationship between markers of inflammation (erythrocyte sedimentation rate [ESR], serum C-reactive protein [CRP] level, serum ADMA) and disease activity.[7] This study in an elegant way has demonstrated (although in a small sample) a statistical association between serum levels of CRP and ESR to disease activity. After the anti-inflammatory therapy, the serum levels of CRP and ESR reduced significantly. The authors were able to see a trend toward an increase in serum ADMA levels compared with baseline after therapy for ARF, but this relationship was not statistically significant. What is intriguing in these findings is that serum levels of ADMA during ARF prior to therapy were lower and this in a way is in contradiction to the previously reported findings of association of serum ADMA with atherosclerosis in the chronic state. There may be a different metabolic response to levels of serum ADMA levels driven by the acuity and intensity of inflammation that may overload the circulating serum antioxidants in contrast to its relationship with a state of chronic low-grade inflammation as seen in coronary atherosclerosis. As the authors also point out, despite a smaller sample size in this study, their findings are intriguing and hypothesis generating, and will need further studies, preferably in prospective manner and multicenter involvement to enroll a larger cohort of patients.

• References

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