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1.
Acta Pharmacol Sin ; 45(7): 1438-1450, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38565961

RESUMO

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.


Assuntos
Movimento Celular , Dinaminas , Células Endoteliais da Veia Umbilical Humana , Subunidade alfa do Fator 1 Induzível por Hipóxia , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial , Quinazolinonas , Espécies Reativas de Oxigênio , Neovascularização Retiniana , Fator A de Crescimento do Endotélio Vascular , Dinâmica Mitocondrial/efeitos dos fármacos , Animais , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Dinaminas/metabolismo , Dinaminas/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo , Quinazolinonas/farmacologia , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologia , Neovascularização Retiniana/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Camundongos , Proliferação de Células/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Angiogênese
2.
Biomedicine (Taipei) ; 9(2): 10, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31124456

RESUMO

BACKGROUND: Various systems have employed with the objective to reduce the time from emergency medical services contact to balloon inflammation for ST-elevation myocardial infraction (STEMI) patients. The WCACG message system was used to an alternative communication platform to improve confirmation of the diagnosis and movement to treatment, resulted in shorten the door-to-balloon (D-to-B) time for STEMI patients. METHODS: We collected 366 STEMI patients admitted at the Sixth Affiliated Hospital of Guangzhou Medical University, Qingyuan People's Hospital, Department of Cardiology, during the period from June 2013 to October 2015. The patients were divided into two groups one underwent the current GC processes and the other group was handled using WCACG system. We compared between two groups with several indicators including D-to-B time, duration of hospitalization, associated costs, and incidence of adverse cardiovascular events. RESULTS: The results show that the new method with WCACG system significantly reduced the average D-to-B time (from 100.42 ± 25.14 mins to 79.81 ± 20.51 mins, P < 0.05) compared to the GC processes, and also reduced the duration, costs and undesirable cardiac incidence during hospitalization. CONCLUSIONS: The modified WCACG process is an applicable system to save pieces of time and efficiently integrate the opinions of experts in emergency.

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