Pulmonary arterial hypertension and the potential roles of metallothioneins: A focused review

Abstract

The pathophysiology of pulmonary arterial hypertension (PAH) is underlined by cell proliferation and vasoconstriction of pulmonary arterioles this involves multiple molecular factors or proteins, but it is not clear what the exact roles of these factors/proteins are. In addition, there may be other factors/proteins that have not been identified that contribute to PAH pathophysiology. Therefore, research has focused on investigating novel role players, in order to facilitate a better understanding of how PAH develop. Evidence suggest that mitochondrial regulators are key role players in PAH pathophysiology, but regulators that have not received sufficient attention in PAH are metallothioneins (MTs). In PAH patients, MT expression is elevated compared to healthy individuals, suggesting that MTs may be possible biomarkers. In other disease-models, MTs have been shown to regulate cell proliferation and vasoconstriction, processes that are instrumental in PAH pathophysiology. Due to the involvement of these processes in PAH pathophysiology and the ability of MTs to modulate them, this paper propose that cellular MTs may also play a role in PAH development. This paper suggests that PAH-research should perhaps begin to investigate the involvement of cellular MTs in the development of PAH.

Keywords: Metallothioneins; Mitochondrial dysfunction; Pulmonary arterial endothelial cell proliferation; Pulmonary arterial hypertension; Pulmonary arterial smooth muscle cells.