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

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.

Calcium Homeostasis, Transporters, and Blockers in Health and Diseases of the Cardiovascular System

“…On the other hand, calcium-permeable ROCCs are recently a subject for the development of specific organic blockers since they were reported to be implicated in neurodegenerative disorders (TRP and AMPA receptors) [100,125,133], mental health (AMPAR), neuropsychiatric disorders (NMDAR) [124], and cardiovascular diseases (NMDA and TRP receptors) [102,109,121]. Recently, the TRPM7 channel was reported to be implicated in pulmonary arterial hypertension [123]. Thus, it would not be surprising if other subtypes of ROCCs are involved in different cardiovascular diseases.…”

“…The TRP channel superfamily includes 28 related non-selective anion channels that display different permeability degrees to calcium classified into six subfamilies: canonical (TRPC), vanilloid TRP (TRPV), melastatin TRP (TRPM), ankyrin TRP, mucolipin TRP, and polycystin TRP [121][122][123]. TRPC channels were the first to be cloned and are intensively studied to this day.…”

The Dysfunction of Ca2+ Channels in Hereditary and Chronic Human Heart Diseases and Experimental Animal Models

“…Thus, TRP channels have broad cardiovascular plasticity. TRPC3, TRPC5, TRPC6, TRPV1, and TRPM7 are involved in the vasoconstriction and regulation of blood pressure and can be considered potential therapeutic targets for the treatment of chronic CVD, including cardiometabolic diseases, and myocardial atrophy [91,119,121,[132][133][134].…”