Abstract
BackgroundHypoxic pulmonary artery hypertension (PAH) as a severe pulmonary disease is characterized by changes of pulmonary vascular reconstruction. Mitochondrial ATP-sensitive potassium channel (mitoKATP) was considered as one of factors responsible for the proliferation of hypoxic pulmonary arterial smooth muscle cells (PASMCs), although the exact mechanisms remain unclear.MethodsPulmonary artery hypertension was induced in rats with or without 5-hydroxydecanoate (5-HD). The mean pulmonary artery pressure, morphologic changes, mRNA and protein expressions of voltage-gated potassium channels (Kv1.5 channel), were measured. The concentrations of monocyte chemo-attractant protein-1 (MCP-1) and transforming growth factor-beta1 (TGF-β1) were detected. Furthermore, pulmonary arterial smooth muscle cells (PASMCs) were isolated and cultured with or without hypoxia pretreated with or without 5-HD or/and Kv1.5 inhibitor 4-aminopyridine (4-AP). Mitochondrial membrane potential (Δψm) and the proliferation of PASMCs were detected.Results5-HD significantly prevented the development of PAH by blocking the mitochondrial membrane depolarization, increased the expression of voltage-gated potassium channels, and reduced pulmonary hypertension mediated by TGF-β1 or MCP-1 signaling pathway.ConclusionThe MitoKATP plays an important role in the development of PAH and may be therapeutic target for the treatment of disease.
Highlights
Hypoxic pulmonary artery hypertension (PAH) as a severe pulmonary disease is characterized by changes of pulmonary vascular reconstruction
Levels of mean pulmonary artery pressure (mPAP) in Hypoxia + V group significantly increased as compared to Controls (p
Histo-pathological examinations of lung tissues revealed that walls of distal pulmonary arteries with positive expression of brown cytoplasm became significantly thickened in Hypoxia + V group, as compared with Controls, which was significantly inhibited by the treatment with 5-HD
Summary
Hypoxic pulmonary artery hypertension (PAH) as a severe pulmonary disease is characterized by changes of pulmonary vascular reconstruction. Mitochondrial ATP-sensitive potassium channel (mitoKATP) was considered as one of factors responsible for the proliferation of hypoxic pulmonary arterial smooth muscle cells (PASMCs), the exact mechanisms remain unclear. The mitoKATP is a key factor in the control of mitochondrial membrane potential (Δψm), which is sensitive to hypoxia. There has not been any reports as to whether mitoKATP plays any important role in vivo, and the studies about the modulation mechanism of mitoKATP on TGF-β and MCP-1 are rarely documented. The present study aims at investigating the important role of mitoKATP in hypoxic-induced PAH in vivo, to measure alterations of Kv1.5 expression, TGF-β1 and MCP-1
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