Exploring the pivotal role of endothelin in rheumatoid arthritis

A chronic inflammatory disorder, rheumatoid arthritis (RA) is an autoimmune and systemic disease characterized by progressive and prolonged destruction of joints. This results in increased mortality, physical disability and destruction. Cardiovascular disorders are one of the primary causes of mortality in patients with RA. It is multifactorial in nature and includes genetic, environmental and demographic factors which contribute to the severity of disease. Endothelin-1 (ET-1) is a peptide which acts as a potent vasoconstrictor and is generated through vascular smooth muscle and endothelial cells. Endothelins may be responsible for RA, as under certain circumstances they produce reactive oxygen species which further promote the production of pro-inflammatory cytokines. This enhances the production of superoxide anion, which activates pro-inflammatory cytokines, resulting in RA. The aim of this review is to elucidate the role of endothelin in the progression of RA. This review also summarizes the natural and synthetic anti-inflammatory drugs which have provided remarkable insights in targeting endothelin.