Hypoxia Induces Proliferation By Activate Na～+/H～+ Exchanger-1 And Through NF-κB Pathway In Pulmonary Arterial Smooth Muscle Cells

Chronic high altitude diseases are compensatory response to hypoxia. chronic obstructive pulmonary disease(COPD) is a respiratory system disease charactered by airflow restricted, however there had no effectual preventive treatments.Both of the diseases have the common pathophysiological change-----hypoxic pulmonaryhypertension (HPH), which includes hypoxic pulmonary vasoconstriction (HPV) and pulmonary vascular structure remodeling (PVSR) resulted from long-term compensatory response. Furthermore the main pathological changes of PVSR are smooth muscle cells hypertrophy and proliferation in pulmonary arteriole media wall induces by hypoxia. Therefore to reveal the mechanism of hypoxia-induced pulmonary artery smooth muscle cells proliferation may find the therapy breakthrough for HPH. Current researches suggest that Na~+/H~+ exchanger-1(NHE-1) generally located in mammalian cell membrane is relevant to proliferation of vascular smooth muscle cells. So we hypothesize hypoxia activates NHE-1 to elevate intracellular pH(pHi), ultimately leads cell proliferation through the certain signal pathways, and thus suppress NHE-1 activity may attenuate HPH.