Abstract:

Objective To investigate the possible signal transduction pathways involved in hypoxia-induced human pulmonary artery smooth muscle cell(HPASMCs) proliferation. Methods Cultured HPASMCs were divided into the following groups, the control group; the hypoxia group(cultured in 3% O₂ for 24 h, 48 h and 72 h) and the treatment groups(hypoxia for 48 h and treated with 2 mmol/L EDTA or 4 μmol/L VIVIT). Cell number was determined with a hemocytometer. ［Ca²⁺］_i was measured by calcium imaging. The translocation of NFATc3 in immunofluorescence-stained HPASMCs was detected by confocal microscopy. Results The cell number, ［Ca²⁺］_i and NFATc3 translocation were significantly higher in hypoxia-treated groups. EDTA(a chelator of Ca²⁺) or VIVIT(the specific inhibitor of NFAT) significantly inhibits the hypoxia-induced proliferation of HPASMCs. Conclusion Ca²⁺-NFAT pathway maybe involved in hypoxia-induced HPASMCs proliferation.

Key words: hypoxia, pulmonary artery smooth muscle cells, pulmonary artery hypertension, capacitative calcium entry, nuclear factor of activated T cells