| First Author | Nagata A | Year | 2020 |
| Journal | Biochem Biophys Res Commun | Volume | 529 |
| Issue | 3 | Pages | 793-798 |
| PubMed ID | 32736709 | Mgi Jnum | J:302388 |
| Mgi Id | MGI:6508237 | Doi | 10.1016/j.bbrc.2020.06.045 |
| Citation | Nagata A, et al. (2020) Genetic knockout and pharmacologic inhibition of NCX1 attenuate hypoxia-induced pulmonary arterial hypertension. Biochem Biophys Res Commun 529(3):793-798 |
| abstractText | The Na(+)/Ca(2+) exchanger type-1 (NCX1) is a bidirectional transporter that is controlled by membrane potential and transmembrane gradients of Na(+) and Ca(2+). Vascular smooth muscle NCX1 plays an important role in intracellular Ca(2+) homeostasis and Ca(2+) signaling. We found that NCX1 was upregulated in the pulmonary arteries of mice exposed to chronic hypoxia (10% O2 for 4 weeks). Hence, we investigated the pathophysiological role of NCX1 in hypoxia-induced pulmonary arterial hypertension (PAH), using NCX1-heterozygous (NCX1(+/-)) mice, in which NCX1 expression is reduced by half, and SEA0400, a specific NCX1 inhibitor. NCX1(+/-) mice exhibited attenuation of hypoxia-induced PAH and right ventricular (RV) hypertrophy compared with wild-type mice. Furthermore, continuous administration of SEA0400 (0.5 mg/kg/day for 4 weeks) to wild-type mice by osmotic pumps significantly suppressed hypoxia-induced PAH and pulmonary vessel muscularization, with a slight reduction in RV hypertrophy. These findings indicate that the upregulation of NCX1 contributes to the development of hypoxia-induced PAH, suggesting that NCX1 inhibition might be a novel approach for the treatment of PAH. |
