Protein Arginine Methyltransferases in Cardiovascular and Neuronal Function

Abstract

The methylation of arginine residues by protein arginine methyltransferases (PRMTs) is a type of post-translational modification which is important for numerous cellular processes, including mRNA splicing, DNA repair, signal transduction, protein interaction, and transport. PRMTs have been extensively associated with various pathologies, including cancer, inflammation, and immunity response. However, the role of PRMTs has not been well described in vascular and neurological function. Aberrant expression of PRMTs can alter its metabolic products, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA). Increased ADMA levels are recognized as an independent risk factor for cardiovascular disease and mortality. Recent studies have provided considerable advances in the development of small-molecule inhibitors of PRMTs to study their function under normal and pathological states. In this review, we aim to elucidate the particular roles of PRMTs in vascular and neuronal function as a potential target for cardiovascular and neurological diseases.

Keywords: ADMA; Arginine methylation; Cardiovascular disease; Neurological disease; Protein arginine methyltransferases; Therapeutic target.

Figure 1.. Protein Arginine Methylation and Nitric Oxide Regulation.

Arginine is the substrate for nitric oxide synthase (NOS) to generate nitric oxide, a regulator of vascular function and homeostasis. Arginine can also be methylated by protein arginine methyltransferases to form asymmetric dimethyl arginine (ADMA) and symmetric dimethylarginine (SDMA). ADMA inhibits the synthesis of nitric oxide, resulting in vascular dysfunction. Cardiovascular disease treatments can employ strategies around impacting PRMT activities and/or ADMA levels.

Figure 2.

Cardiovascular and neurological diseases associated with PRMT dysfunctions.