Exosomes contain a variety of biological active substances such as proteins,miRNAs,lncRNAs and lipids,and exosomes from different cells play different biological functions.Exosomes,as a carrier,are involved in many pa...Exosomes contain a variety of biological active substances such as proteins,miRNAs,lncRNAs and lipids,and exosomes from different cells play different biological functions.Exosomes,as a carrier,are involved in many pathological processes such as nerve injury and repair,vascular regeneration,immune response,and fibrosis formation.It plays an important role in the treatment of eye diseases such as glaucoma,diabetic retinopathy,and keratitis.This paper reviews the research progress of exosomes in various diseases in vivo,which provides a new way for the treatment of eye diseases.展开更多
1 Introduction Effective and timely reperfusion of infarcted coronary artery is crucial to the treatment of patients with ST-segment elevation myocardial infarction(STEMI).[1,2]Current guidelines highly recommend that...1 Introduction Effective and timely reperfusion of infarcted coronary artery is crucial to the treatment of patients with ST-segment elevation myocardial infarction(STEMI).[1,2]Current guidelines highly recommend that the door-to-balloon(D2B)time,as a quality metric of primary percutaneous coronary intervention(PCI)in patients with STEMI,should be≤90 min and preferably less than 60 min.[3,4]However,significant variations from guidelines exist in the real world practices at hospitals.展开更多
Background: Microparticles (MPs) are small extracellular plasma membrane particles shed by activated and apoptotic cells, which are involved in the development of atherosclerosis. Our previous study found that microRN...Background: Microparticles (MPs) are small extracellular plasma membrane particles shed by activated and apoptotic cells, which are involved in the development of atherosclerosis. Our previous study found that microRNA (miR)-19b encapsulated within endothelial MPs (EMPs) may contribute to the upregulation of circulating miR-19b in unstable angina patients. Hypoxia is involved in atherosclerosis as a critical pathological stimulus. However, it still remains unclear whether the increase of miR-19b levels in EMPs is related to hypoxia and if the effect of miR-19b - wrapped within EMPs - stimulates hypoxia on vascular endothelial cells. This study aimed to explore the changes of miR-19b in EMPs induced by hypoxia as well as their effects on endothelial cells.Methods: Human umbilical vein endothelial cells (HUVECs) were culturedin vitro and arranged to harvest EMPs in two parts: the first part consisted of EMPcontrol and EMPhypoxia and the second part included EMPvehicle, EMPNC mimic, and EMPmiR-19b mimic. Cell migration was detected by scratch migration and transwell chamber migration. Angiogenesis was assessed by tube formation assays. Furthermore, we predicted the target gene of miR-19b by bioinformatics analysis, and luciferase assay was used to verify the targeted gene of miR-19b. Data were analyzed by one-way analysis of variance. Student’st-test was used when two groups were compared.Results: Compared with EMPcontrol- and EMPhypoxia-inhibited migration of cells by scratch migration assay (80.77 ± 1.10 vs. 28.37 ± 1.40,P < 0. 001) and transwell chamber migration assay (83.00 ± 3.46 vs. 235.00 ± 16.52,P < 0.01), the number of tube formations was markedly reduced by 70% in the EMPhypoxia group (P < 0.001)in vitro analysis of HUVECs. Meanwhile, a strong inhibition of migration and tube formation of HUVECs in the presence of miR-19b-enriched EMPmiR-19b mimic was observed. This effect might be due to the delivery of miR-19b in EMPs. Transforming growth factor-β2 (TGFβ2) was predicted to be one of the target genes of miR-19b, and we further confirmed thatTGFβ2 was a direct target gene of miR-19b using the luciferase assay. The expression ofTGFβ2 in HUVECs was inhibited by treatment with EMPhypoxia and EMPmiR-19b mimic .Conclusions: MiR-19b in EMPs induced by hypoxia could reduce endothelial cell migration and angiogenesis by downregulating TGFβ2 expression, which may have inhibited the progression of atherosclerosis.展开更多
Background： Apoptosis of endothelial cells （ECs） plays a key role in the development of atherosclerosis and there are also evidence indicated that phosphatase and tensin homolog deleted on chromosome 10 （PTEN） is...Background： Apoptosis of endothelial cells （ECs） plays a key role in the development of atherosclerosis and there are also evidence indicated that phosphatase and tensin homolog deleted on chromosome 10 （PTEN） is a viable target in therapeutic approaches to prevent vascular ECs apoptosis. Aberrant miR-106b-5p expression has been reported in the plasma of patients with unstable atherosclerotic plaques. However, the role and underlying mechanism of miR-106-5p in the genesis of atherosclerosis have not been addressed. In this study, we explored the anti-apoptotic role of miR-106-5p by regulating PTEN expression in vascular ECs. Methods： Real-time reverse transcription polymerase chain reaction （RT-PCR） was performed to detect the expression levels of miR-106b-5p in human atherosclerotic plaques and normal vascular tissues. Human umbilical vein endothelial cells （HUVEC） were transfected with miR-106b-5p mimic or negative control mimic, and apoptosis was induced by serum starvation and tumor necrosis factor-α （TN F-α） treat. Western blotting and real-time RT-PCR experiments were used to detect PTEN expression levels and TN F-α-induced apoptosis was evaluated by the activation of caspase-3 and cell DNA fragmentation levels in HUVEC. Results： The expression ofmiR-106b-5p was significantly downregulated in plaques than in normal vascular tissues. TNF-α significantly downregulated miR-106b-5p expression levels and upregulated activation of caspase-3 and cell DNA fragmentation levels in HUVEC. Overexpression ofmiR-106b-5p with miR-106b-5p mimic inhibited PTEN expression and TNF-α-induced apoptosis in HUVEC. Luciferase reporter assays confirmed that miR-106b-5p binds to PTEN mRNA 3＇ untranslated region site, Conclusion： MiR-106b-5p could inhibit the expression of PTEN in vascular ECs, which could block TNF-α-induced activation of caspase-3, thus prevent ECs apoptosis in atherosclerosis diseases.展开更多
基金Supported by the National Natural Science Foundation of China(No.81470633)the Natural Science Grant of the Heilongjiang Province of China(No.H2018035)the Innovation and Development Foundation of the First Affiliated Hospital of Harbin Medical University(No.2018L002)。
文摘Exosomes contain a variety of biological active substances such as proteins,miRNAs,lncRNAs and lipids,and exosomes from different cells play different biological functions.Exosomes,as a carrier,are involved in many pathological processes such as nerve injury and repair,vascular regeneration,immune response,and fibrosis formation.It plays an important role in the treatment of eye diseases such as glaucoma,diabetic retinopathy,and keratitis.This paper reviews the research progress of exosomes in various diseases in vivo,which provides a new way for the treatment of eye diseases.
基金the National Natural Science Foundation of China(No.81770356&No.81470473)the Capital Health Research and Development of Special(No.2016-2-4083).
文摘1 Introduction Effective and timely reperfusion of infarcted coronary artery is crucial to the treatment of patients with ST-segment elevation myocardial infarction(STEMI).[1,2]Current guidelines highly recommend that the door-to-balloon(D2B)time,as a quality metric of primary percutaneous coronary intervention(PCI)in patients with STEMI,should be≤90 min and preferably less than 60 min.[3,4]However,significant variations from guidelines exist in the real world practices at hospitals.
基金This work was supported by National Natural Science Foundation of China （NSFC） （No. 81400265 and No. 81270274）, and Peking University People＇s Hospital Research and Development funds （RDB2014-16）.
基金grants from the National Natural Science Foundation of China (Nos.81770356, 81470473,and 81600340)and the Capital Health Research and Development of Special (No.2016-2-4083).
文摘Background: Microparticles (MPs) are small extracellular plasma membrane particles shed by activated and apoptotic cells, which are involved in the development of atherosclerosis. Our previous study found that microRNA (miR)-19b encapsulated within endothelial MPs (EMPs) may contribute to the upregulation of circulating miR-19b in unstable angina patients. Hypoxia is involved in atherosclerosis as a critical pathological stimulus. However, it still remains unclear whether the increase of miR-19b levels in EMPs is related to hypoxia and if the effect of miR-19b - wrapped within EMPs - stimulates hypoxia on vascular endothelial cells. This study aimed to explore the changes of miR-19b in EMPs induced by hypoxia as well as their effects on endothelial cells.Methods: Human umbilical vein endothelial cells (HUVECs) were culturedin vitro and arranged to harvest EMPs in two parts: the first part consisted of EMPcontrol and EMPhypoxia and the second part included EMPvehicle, EMPNC mimic, and EMPmiR-19b mimic. Cell migration was detected by scratch migration and transwell chamber migration. Angiogenesis was assessed by tube formation assays. Furthermore, we predicted the target gene of miR-19b by bioinformatics analysis, and luciferase assay was used to verify the targeted gene of miR-19b. Data were analyzed by one-way analysis of variance. Student’st-test was used when two groups were compared.Results: Compared with EMPcontrol- and EMPhypoxia-inhibited migration of cells by scratch migration assay (80.77 ± 1.10 vs. 28.37 ± 1.40,P < 0. 001) and transwell chamber migration assay (83.00 ± 3.46 vs. 235.00 ± 16.52,P < 0.01), the number of tube formations was markedly reduced by 70% in the EMPhypoxia group (P < 0.001)in vitro analysis of HUVECs. Meanwhile, a strong inhibition of migration and tube formation of HUVECs in the presence of miR-19b-enriched EMPmiR-19b mimic was observed. This effect might be due to the delivery of miR-19b in EMPs. Transforming growth factor-β2 (TGFβ2) was predicted to be one of the target genes of miR-19b, and we further confirmed thatTGFβ2 was a direct target gene of miR-19b using the luciferase assay. The expression ofTGFβ2 in HUVECs was inhibited by treatment with EMPhypoxia and EMPmiR-19b mimic .Conclusions: MiR-19b in EMPs induced by hypoxia could reduce endothelial cell migration and angiogenesis by downregulating TGFβ2 expression, which may have inhibited the progression of atherosclerosis.
基金This research was funded by the National Natural Science Foundation of China (NSFC)
文摘Background： Apoptosis of endothelial cells （ECs） plays a key role in the development of atherosclerosis and there are also evidence indicated that phosphatase and tensin homolog deleted on chromosome 10 （PTEN） is a viable target in therapeutic approaches to prevent vascular ECs apoptosis. Aberrant miR-106b-5p expression has been reported in the plasma of patients with unstable atherosclerotic plaques. However, the role and underlying mechanism of miR-106-5p in the genesis of atherosclerosis have not been addressed. In this study, we explored the anti-apoptotic role of miR-106-5p by regulating PTEN expression in vascular ECs. Methods： Real-time reverse transcription polymerase chain reaction （RT-PCR） was performed to detect the expression levels of miR-106b-5p in human atherosclerotic plaques and normal vascular tissues. Human umbilical vein endothelial cells （HUVEC） were transfected with miR-106b-5p mimic or negative control mimic, and apoptosis was induced by serum starvation and tumor necrosis factor-α （TN F-α） treat. Western blotting and real-time RT-PCR experiments were used to detect PTEN expression levels and TN F-α-induced apoptosis was evaluated by the activation of caspase-3 and cell DNA fragmentation levels in HUVEC. Results： The expression ofmiR-106b-5p was significantly downregulated in plaques than in normal vascular tissues. TNF-α significantly downregulated miR-106b-5p expression levels and upregulated activation of caspase-3 and cell DNA fragmentation levels in HUVEC. Overexpression ofmiR-106b-5p with miR-106b-5p mimic inhibited PTEN expression and TNF-α-induced apoptosis in HUVEC. Luciferase reporter assays confirmed that miR-106b-5p binds to PTEN mRNA 3＇ untranslated region site, Conclusion： MiR-106b-5p could inhibit the expression of PTEN in vascular ECs, which could block TNF-α-induced activation of caspase-3, thus prevent ECs apoptosis in atherosclerosis diseases.
