E2F1 Suppresses Oxidative Metabolism and Endothelial Differentiation of Bone Marrow Progenitor Cells

dc.contributor.authorXu, Shiyue
dc.contributor.authorTao, Jun
dc.contributor.authorYang, Liu
dc.contributor.authorZhang, Eric
dc.contributor.authorBoriboun, Chan
dc.contributor.authorZhou, Junlan
dc.contributor.authorSun, Tianjiao
dc.contributor.authorCheng, Min
dc.contributor.authorHuang, Kai
dc.contributor.authorShi, Jiawei
dc.contributor.authorDong, Nian-Guo
dc.contributor.authorLiu, Qinghua
dc.contributor.authorZhao, Ting C.
dc.contributor.authorQiu, Hongyu
dc.contributor.authorHarris, Robert A.
dc.contributor.authorChandel, Navdeep S.
dc.contributor.authorLosordo, Douglas W.
dc.contributor.authorQin, Gangjian
dc.contributor.departmentBiochemistry and Molecular Biology, School of Medicineen_US
dc.date.accessioned2019-08-27T14:12:10Z
dc.date.available2019-08-27T14:12:10Z
dc.date.issued2018-03-02
dc.description.abstractRATIONALE: The majority of current cardiovascular cell therapy trials use bone marrow progenitor cells (BM PCs) and achieve only modest efficacy; the limited potential of these cells to differentiate into endothelial-lineage cells is one of the major barriers to the success of this promising therapy. We have previously reported that the E2F transcription factor 1 (E2F1) is a repressor of revascularization after ischemic injury. OBJECTIVE: We sought to define the role of E2F1 in the regulation of BM PC function. METHODS AND RESULTS: Ablation of E2F1 (E2F1 deficient) in mouse BM PCs increases oxidative metabolism and reduces lactate production, resulting in enhanced endothelial differentiation. The metabolic switch in E2F1-deficient BM PCs is mediated by a reduction in the expression of pyruvate dehydrogenase kinase 4 and pyruvate dehydrogenase kinase 2; overexpression of pyruvate dehydrogenase kinase 4 reverses the enhancement of oxidative metabolism and endothelial differentiation. Deletion of E2F1 in the BM increases the amount of PC-derived endothelial cells in the ischemic myocardium, enhances vascular growth, reduces infarct size, and improves cardiac function after myocardial infarction. CONCLUSION: Our results suggest a novel mechanism by which E2F1 mediates the metabolic control of BM PC differentiation, and strategies that inhibit E2F1 or enhance oxidative metabolism in BM PCs may improve the effectiveness of cell therapy.en_US
dc.eprint.versionAuthor's manuscripten_US
dc.identifier.citationXu, S., Tao, J., Yang, L., Zhang, E., Boriboun, C., Zhou, J., … Qin, G. (2018). E2F1 Suppresses Oxidative Metabolism and Endothelial Differentiation of Bone Marrow Progenitor Cells. Circulation research, 122(5), 701–711. doi:10.1161/CIRCRESAHA.117.311814en_US
dc.identifier.urihttps://hdl.handle.net/1805/20604
dc.language.isoen_USen_US
dc.publisherAmerican Heart Associationen_US
dc.relation.isversionof10.1161/CIRCRESAHA.117.311814en_US
dc.relation.journalCirculation Researchen_US
dc.rightsPublisher Policyen_US
dc.sourcePMCen_US
dc.subjectBone marrowen_US
dc.subjectCell differentiationen_US
dc.subjectEndothelial progenitor cellsen_US
dc.subjectMyocardial infarctionen_US
dc.subjectOxygen consumptionen_US
dc.subjectStem cellsen_US
dc.titleE2F1 Suppresses Oxidative Metabolism and Endothelial Differentiation of Bone Marrow Progenitor Cellsen_US
dc.typeArticleen_US
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