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Editorial
. 2022 Oct 14;131(9):728-730.
doi: 10.1161/CIRCRESAHA.122.321924. Epub 2022 Oct 13.

MonOrail to Cure? Targeting Orai1 to Reverse Pulmonary Arterial Hypertension

Tatiana V Kudryashova  1 , Elena A Goncharova  1
Affiliations
Editorial

MonOrail to Cure? Targeting Orai1 to Reverse Pulmonary Arterial Hypertension

Tatiana V Kudryashova et al. Circ Res. .
No abstract available

Keywords: Editorials; ORAI1 Protein; hypertension, pulmonary; muscle, smooth, vascular; pulmonary artery; translational science, biomedical; vascular remodeling.

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Figures

Figure 1.
Figure 1.. Potential mechanism of Orai1 signaling in pulmonary arterial hypertension.
Left panel: Orai1 is up-regulated in PASMCs in small PAs in human PAH and rat experimental PH. Middle panel: Orai1 up-regulation in PAH PASMCs is triggered by PDGF-Akt-mTOR and hypoxia, and supported by MEK1/2, NFκB, deficiency of KCNK3, and calcineurin-NFAT loop. Orai1 induces SOCE and cytosolic Ca2+ increase, mitochondrial Ca2+ uptake, reduces p21, p38, and cleaved Caspase 9, promotes PASMC proliferation, migration, and apoptosis resistance, pulmonary vascular remodeling, and PH. Right panel: Down-regulation of Orai1 reduces SOCE, mitochondrial Ca2+ uptake, proliferation, migration, and apoptosis resistance of PAH PASMCs. Pharmacological inhibition of Orai1 reduces PH and improves RV in rats with experimental PH. MCT – monocrotaline; mTOR – mechanistic target of rapamycin; PAs – pulmonary arteries; PAH – pulmonary arterial hypertension; PASMCs – pulmonary arterial smooth muscle cells; PDGF – platelet-derived growth factor; PH – pulmonary hypertension; RV – right ventricle; RVSP – RV systolic pressure.
See this image and copyright information in PMC

Comment on

  • Orai1 Inhibitors as Potential Treatments for Pulmonary Arterial Hypertension.
    Masson B, Le Ribeuz H, Sabourin J, Laubry L, Woodhouse E, Foster R, Ruchon Y, Dutheil M, Boët A, Ghigna MR, De Montpreville VT, Mercier O, Beech DJ, Benitah JP, Bailey MA, Humbert M, Montani D, Capuano V, Antigny F. Masson B, et al. Circ Res. 2022 Oct 14;131(9):e102-e119. doi: 10.1161/CIRCRESAHA.122.321041. Epub 2022 Sep 27. Circ Res. 2022. PMID: 36164973

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