Liang Benhui, Lin Wenchao, Tang Yiyang, Li Tangzhiming, Chen Qin, Zhang Wen, Zhou Xinyi, Ma Jiayao, Liu Boqing, Yu Zaixin, Zha Lihuang, Zhang Mengqiu
Department of Cardiology, Xiangya Hospital, Central South University, Changsha, Hunan, China.
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, China.
iScience. 2024 Sep 26;27(10):111036. doi: 10.1016/j.isci.2024.111036. eCollection 2024 Oct 18.
Pulmonary arterial hypertension (PAH) is a life-threatening disease induced by abnormal activation of pulmonary adventitial fibroblasts (PAFs) in the early stage. The association between selenium deficiency and PAH is not yet fully understood. In this study, we found that the serum selenium content of PAH patients was significantly lower than that of healthy volunteers in two independent cohorts. Moreover, PAH patients with lower selenium levels may present poorer prognosis. Prophylactic selenium supplementation could effectively improve hemodynamics and pulmonary vascular remodeling in monocrotaline-induced pulmonary hypertension rat models. Mechanistically, selenium supplementation restored the level of selenium binding protein 1 (SELENBP1) which could exert an antagonistic effect on PAF activation. The rescue assay further proved that selenium supplementation worked in a SELENBP1-dependent manner. These findings demonstrated that selenium deficiency is an important risk factor in PAH, and the selenium-SELENBP1 axis represents a promising target for PAH prevention.
肺动脉高压（PAH）是一种在早期由肺外膜成纤维细胞（PAF）异常激活引起的危及生命的疾病。硒缺乏与PAH之间的关联尚未完全明确。在本研究中，我们发现在两个独立队列中，PAH患者的血清硒含量显著低于健康志愿者。此外，硒水平较低的PAH患者预后可能较差。预防性补充硒可有效改善野百合碱诱导的肺动脉高压大鼠模型的血流动力学和肺血管重塑。从机制上讲，补充硒可恢复硒结合蛋白1（SELENBP1）的水平，该蛋白可对PAF激活发挥拮抗作用。挽救实验进一步证明补充硒以SELENBP1依赖的方式起作用。这些发现表明，硒缺乏是PAH的一个重要危险因素，硒-SELENBP1轴是PAH预防的一个有前景的靶点。
