Role of Store-Operated Ca2+ Entry in the Pulmonary Vascular Remodeling Occurring in Pulmonary Arterial Hypertension

Bastien Masson; David Montani; Marc Humbert; Véronique Capuano; Fabrice Antigny

doi:10.3390/biom11121781

Role of Store-Operated Ca²⁺ Entry in the Pulmonary Vascular Remodeling Occurring in Pulmonary Arterial Hypertension

Biomolecules. 2021 Nov 27;11(12):1781. doi: 10.3390/biom11121781.

Authors

Bastien Masson^{1

2}, David Montani^{1

2

3}, Marc Humbert^{1

2

3}, Véronique Capuano^{1

2

4}, Fabrice Antigny^{1

2}

Affiliations

¹ Faculté de Médecine, School of Medicine, Université Paris-Saclay, 94276 Le Kremlin-Bicêtre, France.
² INSERM UMR_S 999 Pulmonary Hypertension: Pathophysiology and Novel Therapies, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie Lannelongue, 92350 Le Plessis-Robinson, France.
³ Assistance Publique-Hôpitaux de Paris (AP-HP), Department of Respiratory and Intensive Care Medicine, Pulmonary Hypertension National Referral Center, Hôpital Bicêtre, 94276 Le Kremlin-Bicêtre, France.
⁴ Research and Innovation Unit, Groupe Hospitalier Paris Saint-Joseph, Hôpital Marie Lannelongue, 92350 Le Plessis-Robinson, France.

Abstract

Pulmonary arterial hypertension (PAH) is a severe and multifactorial disease. PAH pathogenesis mostly involves pulmonary arterial endothelial and pulmonary arterial smooth muscle cell (PASMC) dysfunction, leading to alterations in pulmonary arterial tone and distal pulmonary vessel obstruction and remodeling. Unfortunately, current PAH therapies are not curative, and therapeutic approaches mostly target endothelial dysfunction, while PASMC dysfunction is under investigation. In PAH, modifications in intracellular Ca²⁺ homoeostasis could partly explain PASMC dysfunction. One of the most crucial actors regulating Ca²⁺ homeostasis is store-operated Ca²⁺ channels, which mediate store-operated Ca²⁺ entry (SOCE). This review focuses on the main actors of SOCE in human and experimental PASMC, their contribution to PAH pathogenesis, and their therapeutic potential in PAH.

Keywords: Ca2+ signaling; IP3R; Orai; PAH; RyR; STIM; TRPC.

Publication types

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

MeSH terms

Calcium Signaling / drug effects
Calcium-Binding Proteins / metabolism*
Clinical Trials as Topic
Gene Expression Regulation / drug effects
Humans
Molecular Targeted Therapy
Pulmonary Arterial Hypertension / drug therapy
Pulmonary Arterial Hypertension / metabolism*
Vascular Remodeling / drug effects

Substances

Calcium-Binding Proteins