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AIM:To analyze the proteins included in exosomes derived from blood of patients with hypertension and seek the main pathologi -cal changes in hypertension .METHODS:Forty-seven patients and healthy subjects were recruited and divided into two comparisons :healthy subjects vs atherosclerosis ( HS vs AS) , and atherosclerosis vs hypertension plus atherosclerosis ( AS vs HT+AS) .We extrac-ted exosomes from blood and utilized LC-MS/MS to identify the protein expression .We used GO analysis to established the hierarchy programs of biological process and molecular function .PPI was used to find the proteins related to the terms .RESULTS:It was found that three final child terms repeatedly shown in BP of the two categories ( HS vs AS and AS vs HT+AS):“signal transduction in re-sponse to DNA damage”,“response to zinc ion”, and“platelet aggregation”.It was found that two final child terms in MF of the two categories:“interleukin 2 receptor binding” and“ploy(A) RNA binding”.The proteins, PSMA6, PSMA7 and CA2, were related to the terms in the two categories .CONCLUSION: We discovered that the exosome proteins may indicate the pathological changes in hypertension through the biological processes related with the specific proteins .These specific proteins, such as VCL, PSMA6, DP, AKAP, ATP5B and CA2, can be the new indicators for severity of hypertension and new therapeutic targets .
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Exosomes secreted by mesenchymal stem cells have shown great therapeutic potential in regenerative medicine .In this study, we performed meta-analysis to assess the clinical effectiveness of using exosomes in ischemia /reperfusion injury based on the reports pub-lished between January 2000 and September 2015 and indexed in the PubMed and Web of Science databases .The effect of exosomes on heart function was evaluated according to the following parameters:the area at risk as a percentage of the left ventricle , infarct size as a percentage of the area at risk , infarct size as a percentage of the left ventricle , left ventricular ejection fraction , left ventricular frac-tion shortening , end-diastolic volume , and end-systolic volume .Our analysis indicated that the currently available evidence confirmed the therapeutic potential of mesenchymal stem cell-secreted exosomes in the improvement of heart function .However , further mechanis-tic studies, therapeutic safety and clinical trials are required for optimization and validation of this approach to cardiac regeneration after ischemia/reperfusion injury .
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AIM:Atherosclerosis primarily involved systemic arteries .Luminal surface , a monolayer of endothelial cells , of artery directly exposes to blood and is susceptible to active substances in the blood .Exosomes contain significantly amount of proteins and RNAs .Ex-osomes can be good and bad for cells , depending on their component .Thus, exosomes may contribute to atherosclerosis by affecting endothelial cells .This study analyzed the relationship of exosome proteins and atherosclerosis .METHODS: Fifty-six patients and healthy subjects were recruited and divided into two comparisons:healthy subjects vs atherosclerosis ( HS vs AS) , and hypertension vs hypertension plus atherosclerosis ( HT vs HT+AS) .Serum exosomes were decoded by protein mass spectrometry .The protein profile and function were analyzed by gene ontology ( GO) .RESULTS:It was found that five child terms repeatedly appeared in “response to stimulus” and “immune system process” of BP of the two categories ( HS vs AS and AS vs HT+AS):“positive regulation of innate immune response”,“immune response-activating signal transduction”,”activation of innate immune response”,“innate immune re-sponse-activating signal transduction” and “innate immune response activating cell surface receptor signaling pathway ”.Two child terms repeatedly showed in “binding” of MF of the two categories:“antigen binding” and “enzyme binding”.Two proteins, PSMA6 and PSMA7, were repeatedly shown in the two categories .CONCLUSION:GO analysis was utilized for structure hierarchy “tree” to illustrate these proteins involved in various terms in BP , CC and MF.The PPI analysis supplied proteins which may play potentially im-portant roles in AS process .Innate immune system and blood coagulation pathway contribute to AS formation .The proteins, PSMA6, PSMA7 and Annexin A2, may can be the new target proteins for prevention and treatment of AS .
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AIM:To investigate the effects of human induced pluripotent stem cell-derived exosomes (hiPSC-exo) on cell viability, capillary-like structure formation , and senescence in endothelial cells exposed to high glucose .METHODS: Exosomes were isolated from the conditional medium of hiPSCs and confirmed by transmission electron microscopy , nanoparticle tracking analysis , and Western blot analysis using Alix and CD63 as markers.hiPSC-exo were labeled with PKH26 for tracking.Cultured HUVECs were treated with high glucose (33 mmol/L) with or without hiPSC-exo (20 mg/L) for 48 h, and cell viability, capillary tube formation, and senescence were assessed .RESULTS:hiPSC-exo showed a typical cup shape and could be taken up by human umbilical vascular endothelial cells (HUVECs) in a concentration-dependent manner.When exposed to high glucose, viability and tube formation in HUVECs was signifi-cantly reduced, whereas the proportion of senescent cells was higher compared to that in control HUVECs (P<0.01).Furthermore, hiPSC-exo restored cell viability and capillary-like structure formation , and reduced senescence in HUVECs exposed to high glucose (P<0.01).However, hiPSC-exo had minimal effects on normal HUVECs.Therefore, stem cell-derived exosomes can promote cell proliferation, enhance capillary-like structure formation , and reduce senescence in endothelial cells exposed to high glucose . CONCLUSION:Our study highlights the role of exosomes derived from hiPSC and may provide a new strategy for maintaining vascular health, preventing vascular aging , and avoiding pathological vascular remodeling that occurs in many diseases .
ABSTRACT
Mesp family proteins comprise two members named mesodermal posterior 1 (Mesp1) and mesodermal posterior 2 (Mesp2). Both Mesp1 and Mesp2 are transcription factors and they share an almost identical basic helix-loop-helix motif. They have been shown to play critical regulating roles in mammalian heart and somite development. Mesp1 sits in the core of the complicated regulatory network for generation of cardiovascular progenitors while Mesp2 is central for somitogenesis. Here we summarize the similarities and differences in their molecular functions during mammalian early mesodermal development and discuss possible future research directions for further study of the functions of Mesp1 and Mesp2. A comprehensive knowledge of molecular functions of Mesp family proteins will eventually help us better understand mammalian heart development and somitogenesis as well as improve the production of specific cell types from pluripotent stem cells for future regenerative therapies.
Subject(s)
Animals , Amino Acid Sequence , Basic Helix-Loop-Helix Transcription Factors , Genetics , Cell Differentiation , Genetics , Gene Expression Regulation, Developmental , Mesoderm , Embryology , Metabolism , Mice, Knockout , Molecular Sequence Data , Pluripotent Stem Cells , Metabolism , Sequence Homology, Amino AcidABSTRACT
[ ABSTRACT] AIM:To determine the role of transcription factor Bach1 in the functions of human microvascular en-dothelial cells ( HMVECs ) .METHODS: Bach1 siRNA was transfected into HMVECs to knock down the expression of Bach1.In vitro endothelial cell tube formation assay in Matrigel culture was used as a surrogate assay for angiogenic poten-tial.Migration of HMVECs was determined by using Transwell chambers.Cell proliferation was measured by CCK-8 assay. Real-time PCR, Western blotting, and ELISA were employed to determine mRNA expression and protein level.Reporter as-say was performed to determine vascular endothelial growth factor ( VEGF) transcriptional activity.RESULTS:Knockdown of Bach1 expression in HMVECs led to an increase in the tube formation and increased endothelial cell migration ability, whereas it has little effect on cell proliferation.Bach1 silencing increased the mRNA and protein expression of heme oxygen-ase-1 (HO-1), and enhanced VEGF transcriptional activation, and mRNA and protein expression.CONCLUSION:Bach1 silencing increases HO-1 and VEGF expression, thus promoting the cell migration and tube formation of HMVECs, indicating that Bach1 is a repressor for angiogenesis.
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Acute fulminant pancreatitis was produced in dogs by injection of autobile into the main pancreatic duct.After injection, the phospholipase A2 (PLA2) activities in serum, lung lymph and bronchoalveolar lavage fluid (BAL) were elevated significantly, lung lymph flow and pulmonary transvascular protein clear ance increased progressively, protein content and cell numbers in BAL were significantly higher than those in control animals.Furthermore, lung index, wet to dry lung weight ratio, extravascular lung water to bloodless dry lung weight ratio increased significantly as compared to control animals.Pretreatment with PLA2 inhibitor, chloroquine,blocked the changes mentioned above.This experiment suggests, (1) PLA2 activity in lung lymph fluid as well as in serum and BAL is elevated in acute hemorrhagic pancreatitis.(2) Elevated PLA2 activity may increase the pulmonary vascular permeability.(3) PLA2 is the major factor leading to pulmonary edema in acute hemorrhagic pancreatits.(4) Phagocytes contribute to the lung injury induced by PLA2 to some extent.
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Intravenous administration of E. coli endotoxin (2mg/kg) caused a persistent increase in platelet activating factor (PAF) contents in arterial blood and bronchoalveolar fluid (BALF). Meanwhile phospholipase A2(PLA2) activity in serum and BALF was elevated and mean arterial blood pressure declined. The total cell number, expecially polymorphonuclear leukocytes and lymphocytes, and protein concentration in BALF were markedly increased 6 h after endotoxin injection. Lung index and extravascular lung water content of endotoxin-treated animals were significantly highter than those of controls. Pretreatment with PAF receptor antagonist SRI 63-441 blocked the increase in PLA, activity and attenuated endotoxin-induced hypotension and acute lung injury. The results suggest that PAF mediates endotoxin-induced lung injury, and leukocyte activation by PAF and the subsequent release of oxygen metabolites and lysoenzymes are important intermediate mechanisms leading to high permeability pulmonary edema.
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The concentration of 1.8 ng/ml platelet activating factor (PAF) caused the elevation of pulmonary vascular permeability and a steady increase of lung weight gain (LWG) in isolated perfused rat lung. The LWG, fluid filtration coefficient and extravasation amount of T-1824 labelled albumin were lower of 89. 2%, 70. 9% and 75. 5%, respectively, in PAF perfusion without Ca2+ group than those in PAF perfusion with Ca2+ group, within 35 min. Mean pulmonary capillary pressure and pulmonary arterial pressure decreased from + 0.725 ? 0.389 kPa and +1.187 ? 0.320 kPa to -0.708 ? 0.315 kPa and - 0.025 ? 0.279 kPa, respectively. Calcium free perfusate without PAF slightly increased vascular permeability in isolated rat lungs. The results suggest that PAF-induced rat lung injury depends on the existence of extracellular calcium ion.