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- W4225615413 abstract "Pulmonary arterial hypertension (PAH) is a severe and progressive disease that leads to right heart failure. The pathogenesis of PAH is generally characterized by vasoconstriction, upregulated proliferation, migration, and pulmonary vascular remodeling in lung tissue. Recent studies using genetic analyses and experimental models have suggested that the hypercontraction of pulmonary arteries induced by Ca2+ signaling abnormality may be involved in the pathogenesis of PAH. However, the pathological functions of Ca2+ transporters in PAH are not clearly understood. The Na+/Ca2+ exchanger type-1 (NCX1) is a bidirectional transporter that is controlled by membrane potential and transmembrane gradients of Na+ and Ca2+. Vascular smooth muscle NCX1 plays an important role in intracellular Ca2+ homeostasis and Ca2+ signaling. In this study, we focused on the pathological role of NCX1 in hypoxia-induced PAH model. Since the expression of NCX1 was markedly increased in the pulmonary arteries of mice exposed to chronic hypoxia, we generated hypoxia-induced PAH model using NCX1 heterozygous knockout mice as well as vascular smooth muscle specific NCX1 conditional knockout mice. Both NCX1 knockout mice exhibited significant reduction in right ventricular systolic pressure and hypertrophy, compared with wild-type mice. In addition, hypoxia-induced pulmonary vessel muscularization was also significantly attenuated in both NCX1 knockout mice. Furthermore, specific NCX1 inhibitor SEA0400 significantly suppressed hypoxia-induced PAH and pulmonary vessel muscularization, with a slight reduction in right ventricular hypertrophy in wild-type mice. These findings indicate that the upregulation of vascular smooth muscle NCX1 contributes to the development of hypoxia-induced PAH, suggesting that NCX1 inhibition might be a novel approach for the treatment of PAH." @default.
- W4225615413 created "2022-05-05" @default.
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- W4225615413 date "2022-01-01" @default.
- W4225615413 modified "2023-10-16" @default.
- W4225615413 title "Therapeutic strategy targeting NCX1 for pulmonary arterial hypertension" @default.
- W4225615413 doi "https://doi.org/10.1254/jpssuppl.95.0_3-s41-3" @default.
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