Potential of the TRPM7 channel as a novel therapeutic target for pulmonary arterial hypertension

J Smooth Muscle Res. 2022;58(0):50-62. doi: 10.1540/jsmr.58.50.

Abstract

Pulmonary arterial hypertension (PAH) is an intractable vascular disease characterized by a progressive increase in pulmonary vascular resistance caused by pulmonary vascular remodeling, which ultimately leads to right-sided heart failure. PAH remains incurable, despite the development of PAH-targeted therapeutics centered on pulmonary artery relaxants. It is necessary to identify the target molecules that contribute to pulmonary artery remodeling. Transient receptor potential (TRP) channels have been suggested to modulate pulmonary artery remodeling. Our study focused on the transient receptor potential ion channel subfamily M, member 7, or the TRPM7 channel, which modulates endothelial-to-mesenchymal transition and smooth muscle proliferation in the pulmonary artery. In this review, we summarize the role and expression profile of TRPM7 channels in PAH progression and discuss TRPM7 channels as possible therapeutic targets. In addition, we discuss the therapeutic effect of a Chinese herbal medicine, Ophiocordyceps sinensis (OCS), on PAH progression, which partly involves TRPM7 inhibition.

Keywords: TRPM7; cardiovascular remodeling; pulmonary arterial hypertension.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Proliferation
  • Familial Primary Pulmonary Hypertension / metabolism
  • Humans
  • Hypertension, Pulmonary* / drug therapy
  • Hypertension, Pulmonary* / metabolism
  • Myocytes, Smooth Muscle / metabolism
  • Protein Serine-Threonine Kinases
  • Pulmonary Arterial Hypertension* / drug therapy
  • Pulmonary Artery / metabolism
  • TRPM Cation Channels* / metabolism
  • Transient Receptor Potential Channels* / metabolism
  • Transient Receptor Potential Channels* / therapeutic use
  • Vascular Remodeling

Substances

  • TRPM Cation Channels
  • Transient Receptor Potential Channels
  • Protein Serine-Threonine Kinases
  • TRPM7 protein, human