Arginine Derivatives in Cerebrovascular Diseases: Mechanisms and Clinical Implications

Abstract

The amino acid L-arginine serves as substrate for the nitric oxide synthase which is crucial in vascular function and disease. Derivatives of arginine, such as asymmetric (ADMA) and symmetric dimethylarginine (SDMA), are regarded as markers of endothelial dysfunction and have been implicated in vascular disorders. While there is a variety of studies consolidating ADMA as biomarker of cerebrovascular risk, morbidity and mortality, SDMA is currently emerging as an interesting metabolite with distinct characteristics in ischemic stroke. In contrast to dimethylarginines, homoarginine is inversely associated with adverse events and mortality in cerebrovascular diseases and might constitute a modifiable protective risk factor. This review aims to provide an overview of the current evidence for the pathophysiological role of arginine derivatives in cerebrovascular ischemic diseases. We discuss the complex mechanisms of arginine metabolism in health and disease and its potential clinical implications in diverse aspects of ischemic stroke.

Keywords: ADMA; ESUS; SDMA; arginine; atherosclerosis; atrial fibrillation; biomarker; endothelial dysfunction; homoarginine; stroke.

Figure 1

Overview on metabolism of arginine (Arg), homoarginine (hArg), asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and monomethylarginine (NMMA) as well as putative links to cerebrovascular risk and disease. Prohibition signs besides lines refer to an inhibitory relation. For further explanation see Section 2. The figure was created using BioRender.