钾通道与肺动脉平滑肌细胞凋亡

钾通道与肺动脉平滑肌细胞的生长、增殖和凋亡密切相关.在肺动脉高压的发生、发展中起着重要作用.肺动脉平滑肌细胞膜钾通道活性降低或表达下降不仅导致细胞浆游离Ca2+浓度升高,肺动脉平滑肌细胞收缩、增殖和肺血管重构,而且也与肺动脉平滑肌细胞凋亡减少有关.凋亡性容积减少是细胞凋亡的必要前提和早期标志.钾通道参与凋亡性容积减少调节、细胞色素C释放、Caspase激活和DNA降解等凋亡事件以及抗凋亡蛋白Bcl-2、survivin的调节.因此.钾通道有望成为诱导肺动脉平滑肌细胞凋亡药物的靶点,为未来攻克肺动脉高压带来新希望.

K+ channels and pulmonary artery smooth muscle cell apoptosis

K+ channels are involved in the growth, proliferation and apoptosis of pulmonary artery smooth muscle cell (PASMC), and play an important role in the development of pulmonary artery hypertension. Decreased K+ channel function and expression not only stimulate PASMC contraction, proliferation and pulmonary vascular remodeling by increasing Ca2+ concentration in cytoplasm, but also inhibit PASMC apoptosis. Apoptotic volume decrease is an early mark and prerequisite of apoptosis. KK+ channels are involved in regulation of apoptotic volume decrease,cytochrome C release, caspase activation, DNA fragmentation and regulation of antiapoptic protein Bcl-2 and survivin. Therefore,K+ channels may be targeted to develop therapeutic approaches for induction or enhancement of PASMC apoptosis, which remains an exciting possibility for management of pulmonary artery hypertension in future.