Protective Mechanism Of Fluoxetine On The Imbalance Between Proliferation And Apoptosis In ET-1Induced Human Pulmonary Arterial Smooth Cells

Purpose:Pulmonary Kv channels are thought to play a crucial role in the regulation of cell proliferation and apoptosis. The previous studies have shown that fluoxetine upregulate the expression of Kv1.5and prevent pulmonary arterial hypertension in monocrotaline-induced or hypoxia-induced rats and mice. The current study was designed to test how fluoxetine regulate Kvl.5channel and subsequently promoting apoptosis in Human PASMCs cultured in vitro.Methods:The human PASMCs were incubated with low-serum DMEM, ET-1, fluoxetine with and without ET-1separately for72h. then the proliferation and apoptosis, expession of TRPC1,Caspase-3,Bcl-2,Bcl-xl and kv1.5were detected.Results:In ET-1indued group, the upregulation of TRPC1(1.2448±0.2157vs0.6572±0.1076, P<0.01) and down regulation of Kv(1.51.2198±0.1016vs2.5717±0.1557, P<0.001) enhance the proliferation and anti-apoptosis(1.1±0.1634vs2.3834±0.0703, P<0.01), and which was reversed, treated with fluoxetine. The decreased expression of TRPC1(0.7904±0.1043vs1.2448±0.2157, P<0.05) increaed the Kv1.5(2.1234±0.1766vs1.2198±0.1016, P<0.001), subsequently inhibiting the proliferation and promoting apoptosis(4.85±0.3852vs1.1±0.1634,P<0.001).Conclusions:The results from the present suggest that fluoxetine protects against big Endothelin-1induced anti-apoptosis and rescues Kvl.5channels in human pulmonary arterial smooth muscle cells potentially by decreasing the intracellular Ca2+concentration.