Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deep venous thrombosis (DVT) is one of the most common peripheral vascular diseases. The roles of bone marrow-derived endothelial progenitor cells (EPCs) on the recanalization of venous thrombosis has been suggested recently, while the underlying mechanisms are not completely understood. Our objective was to investigate the functions of autophagy protein 5 (ATG5) in rat EPCs and its potential application in DVT. We have found that silencing of ATG5 or pharmacological suppression of ATG5 in rat EPCs reduces both the migration and psudotube formation under hypoxia in vitro. In line, overexpression of ATG5 significantly enhances the EPCs migration and psudotube formation capabilities. More importantly, injection of EPCs that stably express ATG5 increases EPC homing to the ischemic site and promotes thrombus recanalization in a rat DVT model in vivo. Mechanistically, we have shown that ATG5 overexpression enhances psudotube formation via the activation of AKT. These findings suggest that ATG5-AKT signaling plays an essential role in EPC migration and psudotube formation. Regulation of ATG5-AKT signaling may provide a potential novel therapy for DVT.
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PMID:Autophagy protein 5 enhances the function of rat EPCs and promotes EPCs homing and thrombus recanalization via activating AKT. 2625 Oct 76

The development of deep venous thrombosis (DVT) is a sterile inflammatory process related to cytokines, such as interleukin (IL)-6 or IL-17. IL-9 is a cytokine involved in many inflammatory diseases, including cystic fibrosis, ulcerative colitis, psoriasis and psoriatic arthritis. However, it remains unknown whether IL-9 is related to DVT. In this study, we characterized the role and mechanism of IL-9 in DVT. Analysis of the data of patients with and without DVT revealed that stasis, venous surgery as well as elevated IL-9 and sP-selectin levels were related to the development of DVT. We also showed for the first time that IL-9 receptor was expressed in mouse platelets, and it dramatically promoted the aggregation rate and expression of P-selectin (CD62P) in the presence of adenosine diphosphate, but otherwise exhibited no effect on platelets. This study also revealed that Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signalling pathway, not phosphoinositide 3-kinase/AKT pathway, was involved in the process. We also showed in a mouse model of stasis that the thrombus size (weight and length) and CD62P expression in the thrombus were higher and lower in the IL-9 group and IL-9 antibody group, respectively, than in the control group. All these findings indicated that IL-9 facilitated platelet function through the JAK2/STAT3 pathway, thus promoting the development of DVT.
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PMID:IL-9 Promotes the Development of Deep Venous Thrombosis by Facilitating Platelet Function. 3030 Sep 11

Endothelial progenitor cells are recognized as the potential targets for the revascularization and angiogenesis because of their ability to get themselves transformed into mature endothelial cells. Underlying pathophysiology in diabetes mellitus leads to decrease in circulatory endothelial progenitor cells, resulting in diabetic macro-vascular and micro-vascular complications. Peroxisome Proliferator Activated Receptor (PPAR) gamma analogues serves as an effective therapy for controlling blood sugar levels and preventing its complications. Reports of clinical trials and meta-analysis of clinical trial suggests the beneficial aspects of PPAR gamma therapy in increasing the number and function of circulating endothelial progenitor cells. This review highlights the pleotropic effect of PPAR gamma analogs, apart from their antidiabetic action via reduction of oxidative stress, increasing expression of eNOS, reducing level of miR 22, miR 222 levels and positive modulation of rapamycin/Protein kinase B/phosphoinoside3-kinase pathways, preventing the early apoptosis, enhanced mobility proliferation and transformation into mature endothelial cells. PPAR gamma therapy in diabetes regulates endothelial progenitor cells, reduces complications of diabetes like retinopathy, nephropathy, neuropathy, cardiomyopathy, deep vein thrombosis, and maintains the healthy vasculature.
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PMID:Potential role of Peroxisome Proliferator Activated Receptor gamma analogues in regulation of endothelial progenitor cells in diabetes mellitus: An overview. 3133 54

We have previously reported that miR-9 promotes the homing, proliferation, and angiogenesis of endothelial progenitor cells (EPCs) by targeting transient receptor potential melastatin 7 via the AKT autophagy pathway. In this way, miR-9 promotes thrombolysis and recanalization following deep vein thrombosis (DVT). However, the influence of miR-9 on messenger RNA (mRNA) expression profiles of EPCs remains unclear. The current study comprises a comprehensive exploration of the mechanisms underlying the miR-9-regulated angiogenesis of EPCs and highlights potential treatment strategies for DVT. We performed RNA sequence analysis, which revealed that 4068 mRNAs were differentially expressed between EPCs overexpressing miR-9 and the negative control group, of which 1894 were upregulated and 2174 were downregulated. Gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses indicated that these mRNAs were mainly involved in regulating cell proliferation/migration processes/pathways and the autophagy pathway, both of which represent potential EPC-based treatment strategies for DVT. Reverse transcriptase quantitative polymerase chain reaction confirmed the changes in mRNA expression related to EPC angiogenesis, migration, and autophagy. We also demonstrate that miR-9 promotes EPC migration and angiogenesis by regulating FGF5 directly or indirectly. In summary, miR-9 enhances the expression of VEGFA, FGF5, FGF12, MMP2, MMP7, MMP10, MMP11, MMP24, and ATG7, which influences EPC migration, angiogenesis, and autophagy. We provide a comprehensive evaluation of the miR-9-regulated mRNA expression in EPCs and highlight potential targets for the development of new therapeutic interventions for DVT.
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PMID:Clarification of the Role of miR-9 in the Angiogenesis, Migration, and Autophagy of Endothelial Progenitor Cells Through RNA Sequence Analysis. 3302 8