A role of miRNA in pulmonary arterial hypertension / 国际儿科学杂志

Pulmonary hypertension is characterized by the progressive increase of pulmonary arterial pressure and the gradually increasing of pulmonary vascular resistance,leading to a common disease of right heart failure and death.The pathogenesis of pulmonary hypertension has not yet been fully elucidated.The pathological feature of pulmonary arterial hypertension is the pulmonary vascular remodeling including vascular endothelial cell injury,smooth muscle cell proliferation,migration and deposition of extracellular matrix.MicroRNA is an endogenous nucleotide fragment,which can activate the expression of genes related to signal transduction through the corresponding biological behavior.Recent studies have found that microRNA plays an important role in pulmonary arterial hypertension through the injury of vascular endothelial cells,smooth muscle cell proliferation,migration and extracellular matrixdeposition.The research about microRNA that participates in the mechanism of pulmonary arterial hypertension provides a new theoretical basis for the prevention and treatment of pulmonary arterial hypertension.This review focuses on progress of microRNA and the mechanisms of pulmonary arterial hypertension.

Expression of P-MLCK in human pulmonary arterial endothelial cell induced by lipopolysaccharide / 上海第二医科大学学报

Objective To study the expression of phosphorylated myosin light chain kinase(P-MLCK) in human pulmonary arterial endothelial cell(HPAEC) induced by lipopolysaccharide(LPS). Methods HPAECs were cultured in vitro and treated with LPS(2 ?g/mL) and normal saline for 1 h,respectively.Immunofluorescence method and western blotting were used to detect P-MLCK. Results Compared with normal saline group,the number of HPAECs decreased,but the morphology of cells did not change.After treatment of LPS for 30 and 60 min,the expression of P-MLCK in HPAEC increased from 0.41?0.05 to 0.82?0.43 and 1.56?0.07,respectively(P

The effect of cytokines and endotoxin on the nitric oxide production and its relation to mitochondrial aconitase activity in cultured rat lung microvascular endothelial cells / 대한내과학회지

OBJECTIVE: Both constitutive and inducible forms of nitric oxide synthase exist in endothelial cells. Disorders that produce acute lung injury frequently release endotoxin and cytoknes, such as interferon(IFNgamma) and tumor necrosis factor (TNFalpha). Endotoxin and these cytokines likely act as important mediators of cell injury. Because nitric oxide (NO) avidly reacts with iron, it may affect the activity of key enzymes, such as mitochondrial aconitase, which contain an iron-sulfur structure as a prosthetic group. METHOD: We studied the effect of IFNgamma, TNFalpha and E. coli lipopolysaccharide(LPS) on NO production and mitochondrial aconitase activity in cultured rat lung microvascular endothelial cells(RLMVC). RESULT: Exposing RLMVC for 24 hours to IFNgamma(500 U/mL), TNFalpha(300 U/mL) and LPS(5 microgram/mL) significantly increases nitrite production to 20+/-1 micrometer compared to 0.07 micrometer in control cells(P<0.05, n=4). Cytokine treatment also reduced mitochondrial aconitase activity from 196+/-8 to 102+/-34 nmole/min/mg of cell protein(P<0.05, n=4). Treatment with the inhibitor of nitric oxide synthase N-monomethyl-L-arginine(NMMA) (0.5 mM) not only significantly blunted the cytokine-mediated increase in nitrite formation (3+/-0.5 micrometer vs 20+/-1 micrometer with cytokines, P<0.05, n=4), but also prevented the cytokine-mediated drop in aconitase activity (161+/- 24 vs. 196+/-8 nmole/min/mg of cell protein, NS). CONCLUSION: Exposing RLMVC to IFNgamma, TNFalpha and E. coli LPS substantially decreases mitochondrial aconitase activity. Nitric oxide appears to mediate this effect. Our results suggest that the excessive production of NO by endothelial cells, in response to cytokines and endotoxin, may inhibit the function of the endothelial cell itself.