Orai1/STIMs modulators in pulmonary vascular diseases

Anaïs Saint-Martin Willer; David Montani; Véronique Capuano; Fabrice Antigny

doi:10.1016/j.ceca.2024.102892

Orai1/STIMs modulators in pulmonary vascular diseases

Cell Calcium. 2024 Apr 24:121:102892. doi: 10.1016/j.ceca.2024.102892. Online ahead of print.

Authors

Anaïs Saint-Martin Willer¹, David Montani², Véronique Capuano³, Fabrice Antigny⁴

Affiliations

¹ Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; INSERM UMR_S 999 Hypertension pulmonaire: Physiopathologie et Innovation Thérapeutique, Hôpital Marie Lannelongue, Le Plessis-Robinson, France.
² Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; INSERM UMR_S 999 Hypertension pulmonaire: Physiopathologie et Innovation Thérapeutique, Hôpital Marie Lannelongue, Le Plessis-Robinson, France; Assistance Publique - Hôpitaux de Paris (AP-HP), Service de Pneumologie et Soins Intensifs Respiratoires, Centre de Référence de l'Hypertension Pulmonaire, Hôpital Bicêtre, Le Kremlin-Bicêtre, France.
³ Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; INSERM UMR_S 999 Hypertension pulmonaire: Physiopathologie et Innovation Thérapeutique, Hôpital Marie Lannelongue, Le Plessis-Robinson, France; Hôptal Marie Lannelongue, Groupe Hospitalier Paris Saint-Joseph, Le Plessis-Robinson, France.
⁴ Université Paris-Saclay, Faculté de Médecine, Le Kremlin-Bicêtre, France; INSERM UMR_S 999 Hypertension pulmonaire: Physiopathologie et Innovation Thérapeutique, Hôpital Marie Lannelongue, Le Plessis-Robinson, France. Electronic address: fabrice.antigny@inserm.fr.

PMID: 38735127
DOI: 10.1016/j.ceca.2024.102892

Abstract

Calcium (Ca²⁺) is a secondary messenger that regulates various cellular processes. However, Ca²⁺ mishandling could lead to pathological conditions. Orai1 is a Ca²⁺channel contributing to the store-operated calcium entry (SOCE) and plays a critical role in Ca²⁺ homeostasis in several cell types. Dysregulation of Orai1 contributed to severe combined immune deficiency syndrome, some cancers, pulmonary arterial hypertension (PAH), and other cardiorespiratory diseases. During its activation process, Orai1 is mainly regulated by stromal interacting molecule (STIM) proteins, especially STIM1; however, many other regulatory partners have also been recently described. Increasing knowledge about these regulatory partners provides a better view of the downstream signalling pathways of SOCE and offers an excellent opportunity to decipher Orai1 dysregulation in these diseases. These proteins participate in other cellular functions, making them attractive therapeutic targets. This review mainly focuses on Orai1 regulatory partners in the physiological and pathological conditions of the pulmonary circulation and inflammation.

Keywords: Cardiac; Inflammation; Pulmonary circulation; Regulatory proteins of SOCE; SOCE.

Publication types

Review