RESUMEN
Pulmonary hypertension(PH)is the pulmonary vascular remodeling caused by endothe-lial dysfunction and other factors,which leads to the increase of pulmonary artery pressure and finally right heart failure and patient death.Medications can significantly improve the symptoms of patients with pulmonary hypertension,but drugs can't cure vascular remodeling and right heart failure once for all,so it is urgent to find new treatments.Endothelial cells can obtain mesenchymal phenotypes after hypoxia stimulation,that is,endothelial-to-mesenchymal transition(EndMT).Increasing studies have shown that EndMT plays an important role in pulmonary vascular remodeling of PH.In this review,three signaling pathways related to induction of endothelial-to-mesenchymal transition under hypoxic conditions and research progress in related drugs are elaborated:① Transforming growth factor-β/bone morphogenetic protein(TGF-β/BMP)signaling pathway.The TGF-β/BMP pathway is mediated by Smad,and hypoxia regulates the expressions of EndMT-related genes by inhibiting or inducing the phosphorylation level of Smad in the downstream medium.② Notch signaling pathway.Hypoxia can enhance Jagged/Notch signaling pathway and promote the EndMT process.③Wnt/β-catenin signaling pathway.Hypoxia increases the expression of β-catenin,activates the Wnt signaling pathway,and regulates the expressions of EndMT regulatory genes.The significance of hypoxia-induced EndMT as an impor-tant pathogenic factor in PH is clarified in order to provide new ideas for the improvement of pulmonary vascular remodeling and recommend new effective strategies for the prevention and treatment of PH.
RESUMEN
Aim To investigate the effect of orientin on proliferation and differentiation of 3T3-L1 pre-adipocytes and on insulin resistance(IR) in 3T3-L1 adipocytes and the possible mechanisms.Methods MTT assay and oil red O staining were applied to investigate the proliferation and the differentiation of 3T3-L1 pre-adipocytes, respectively.The intracellular triglyceride(TG) contents were detected by enzymatic analysis.IR model was induced with dexamethasone.A fluorescent glucose analogue, 2-NBDG, was used to measure the rate of glucose uptake.Western blot was used to detect the protein level of GLUT4 and phosphorylation of AMPK and ACC.The GLUT4 translocation was measured by fluorescent-immunohistochemistry.Results Orientin decreased the formation of lipid droplets and intracellular TG contents(P<0.01) in a concentration-dependent manner(P<0.05), but it had no obvious effects on the cell vitality.Under the IR state, orientin significantly increased 3T3-L1 adipocytes glucose uptake(P<0.05).Meanwhile, orientin up-regulated the protein expression of p-AMPK, p-ACC, and enhanced GLUT4 translocation and its expression.Conclusion Orientin can effectively inhibit the differentiation of 3T3-L1 pre-adipocytes and increase insulin sensitivity due to the activation of AMPK/GLUT4 signal pathway.
RESUMEN
Sustained hypoxic pulmonary vasoconstriction (HPV ) as experienced at high altitude can lead to hypoxic pulmonary hypertension(HPH).HPV,a special physiological phenomenon of lung,is the physiological reflex of organism in hypoxic envi-ronment.However,in high altitude hypoxic environment,the sustained HPV can lead to pulmonary vascular remodeling and right ventricular hypertrophy,at the same time,the degree of hypoxia in alveoli can be aggravated.Vicious circle of hypoxia is formed,further causing the severe high altitude sickness such as pulmonary edema and pulmonary heart disease.HPV appears in preliminary of HPH,but in the chronic phase,irreversible hy-poxic pulmonary vascular remodeling forms.Therefore,studying the mechanism of HPV and the effect of HPV in HPH can pro-vide targets and ideas for the prevention and treatment of high al-titude sickness. Additionally, in preliminary stage of HPV, prompt treatment is critical for the prevention of high altitude sickness.However,the mechanism of HPV and its roles in HPH are still not fully elucidated in current studies.This paper sum-marizes the studies about HPV in HPH of recent years,aiming to provide references for researchers and clinical treatment in this research field.