• Home
  • Search Results
  • Apigenin attenuates pulmonary hypertension by inducing mitochondria-dependent apoptosis of PASMCs via inhibiting the hypoxia inducible factor 1α-KV1.5 channel pathway.

Apigenin attenuates pulmonary hypertension by inducing mitochondria-dependent apoptosis of PASMCs via inhibiting the hypoxia inducible factor 1α-KV1.5 channel pathway.

Chemico-biological interactions (2020-01-14)
Yuanzhou He, Xiaoyu Fang, Jing Shi, Xiaochen Li, Min Xie, Xiansheng Liu
ABSTRACT

Pulmonary hypertension (PH) is distal pulmonary arterial remodelling and is mainly due to the abnormal proliferation and apoptosis resistance of pulmonary artery smooth muscle cells (PASMCs). Apigenin, a natural dietary flavonoid, is a promising PH preventive agent that inhibits PASMC proliferation and induces apoptosis. In this study, we investigated the biological effects of apigenin on PH. PH was induced in male Sprague-Dawley rats by chronic hypoxia exposure. Administration of apigenin prevented the development of PH, hypoxia-induced right ventricular hypertrophy and pulmonary arterial remodelling and prevented the progression of established PH in this model. Moreover, treatment with apigenin induced mitochondria-dependent apoptosis. To explore the underlying mechanisms, the mitochondrial membrane potential (Δψm) and the mitochondria-dependent apoptosis factors cytochrome C, BAX, Bcl-2, cleaved caspase 3, and cleaved caspase 9 were analysed. These results confirmed that apigenin induces mitochondria-dependent apoptosis in hypoxic PASMCs to protect against PH. In addition, treatment with apigenin reversed hypoxia-induced inhibition of KV1.5 expression both in vivo and in vitro. The KV1.5 inhibitor diphenyl phosphine oxide-1 (DPO-1) abrogated apigenin-induced mitochondria-dependent apoptosis in hypoxic PASMCs, suggesting that KV1.5 is implicated in apigenin-induced mitochondria-dependent apoptosis. Furthermore, functional studies revealed that apigenin activated mitochondria-dependent apoptosis by modulation of hypoxia-induced factor 1α (HIF-1α) signalling. Together, our study shows that apigenin attenuates PH via inhibiting the HIF-1α-KV1.5 channel pathway to induce PASMC mitochondria-dependent apoptosis.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Diphenylphosphine, 98%
Sigma-Aldrich
Tetramethylrhodamine methyl ester perchlorate, ≥95%
Sigma-Aldrich
DPO-1, needles, >97% (NMR)