MonOrail to Cure? Targeting Orai1 to Reverse Pulmonary Arterial Hypertension

Abstract

ulmonary arterial hypertension (PAH) is a progressive and rapidly fatal disease with no cure. In PAH, increased pulmonary vascular resistance and mean pulmonary arterial (PA) pressure (≥20 mmHg at rest) due to vasoconstriction and remodeling of small PAs leads to elevation of right ventricle (RV) afterload and premature death of right heart failure. 1 Over the last decades, development of new therapeutic options significantly improved patients' outcomes. However, available therapies, predominantly vasodilators, do not reverse pulmonary vascular remodeling or stop disease progression, and PAH remains a life-limiting disease with high mortality rates and no curative therapeutic options. 2

Pregnancy-Specific Beta-1-Glycoprotein 1 Increases HTR-8/SVneo Cell Migration through the Orai1/Akt Signaling Pathway

“…Numerous investigations have demonstrated the involvement of SOCE-related proteins, such as Orais and STIM1, in signaling pathways associated with both normal and pathological processes. For example, Orai1-mediated SOCE is involved in the formation and development of pulmonary hypertension [ 40 , 41 , 42 ]. In the present study, we found that PSG1 at a concentration of 0.1 μg/mL had the ability to increase the Orai1 protein expression in the HTR-8/SVneo cells, ultimately promoting the migration of the HTR-8/SVneo cells.…”