Leifheit-Nestler, Maren

[["dc.bibliographiccitation.firstpage","200"],["dc.bibliographiccitation.issue","2"],["dc.bibliographiccitation.journal","Arteriosclerosis, Thrombosis, and Vascular Biology"],["dc.bibliographiccitation.lastpage","206"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Heida, Nana-Maria"],["dc.contributor.author","Leifheit-Nestler, Maren"],["dc.contributor.author","Schroeter, Marco R."],["dc.contributor.author","Mueller, Jan-Peter"],["dc.contributor.author","Cheng, I-Fen"],["dc.contributor.author","Henkel, Sarah"],["dc.contributor.author","Limbourg, Anne"],["dc.contributor.author","Limbourg, Florian P."],["dc.contributor.author","Alves, Frauke"],["dc.contributor.author","Quigley, James P."],["dc.contributor.author","Ruggeri, Zaverio M."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Konstantinides, Stavros"],["dc.contributor.author","Schaefer, Katrin"],["dc.date.accessioned","2017-09-07T11:46:10Z"],["dc.date.available","2017-09-07T11:46:10Z"],["dc.date.issued","2010"],["dc.description.abstract","Objective-To investigate the capacity of the adipokine leptin to promote angiogenesis by modulating the function of circulating angiogenic cells (CACs). Methods and Results-In vitro, leptin specifically promoted CAC adhesion to tubular endothelial structures and migration along outgrowing sprouts of endothelial cells. In vivo, stimulation of CACs with leptin increased their capacity to promote new vessel formation in the chorioallantoic membrane of chicken embryos and to improve neovascularization of ischemic murine hind limbs. These effects required the phosphorylation of alpha v beta 5 integrins, which depended on the interaction of leptin with its receptor ObR, and on Janus kinase (JAK) 2- and phospholipase C (PLC) gamma-mediated activation of Src kinase. Protein tyrosine phosphatase 1B, a negative regulator of leptin signaling, was overexpressed in CACs from obese, hyperleptinemic individuals, and this was associated with insensitivity of CACs to the angiogenic effects of leptin. Weight loss (by 30 +/- 15 kg) normalized protein tyrosine phosphatase 1B expression in CACs and restored their responsiveness to leptin. A similar dose- dependent response was found after incubation of CACs from obese subjects with a protein tyrosine phosphatase 1B inhibitor ex vivo. Conclusion-Our results point to the ObR-Src kinase-alpha v beta 5 cross talk as a distinct novel component of the network of specific interactions between integrins and cytokine receptors in angiogenesis. (Arterioscler Thromb Vasc Biol. 2010; 30: 200-206.)"],["dc.identifier.doi","10.1161/ATVBAHA.109.192807"],["dc.identifier.gro","3142969"],["dc.identifier.isi","000273799900014"],["dc.identifier.pmid","19910644"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/431"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: National Institutes of Health [NIH HL-75736]"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1079-5642"],["dc.title","Leptin Enhances the Potency of Circulating Angiogenic Cells Via Src Kinase and Integrin alpha v beta 5 Implications for Angiogenesis in Human Obesity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.issue","21"],["dc.bibliographiccitation.journal","Circulation"],["dc.bibliographiccitation.volume","122"],["dc.contributor.author","Schroeter, M. R."],["dc.contributor.author","Stein, Susanne"],["dc.contributor.author","Heida, Nana-Maria"],["dc.contributor.author","Leifheit-Nestler, Maren"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Cheng, I-Fen"],["dc.contributor.author","Shah, Ajay M."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Konstantinides, Stavros V."],["dc.contributor.author","Schaefer, Katrin"],["dc.date.accessioned","2018-11-07T08:36:40Z"],["dc.date.available","2018-11-07T08:36:40Z"],["dc.date.issued","2010"],["dc.identifier.isi","000208231600521"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/18371"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.publisher.place","Philadelphia"],["dc.relation.issn","0009-7322"],["dc.title","Leptin Promotes the Mobilization of Fetal Liver Kinase 1-Positive Vascular Progenitor Cells From the Bone Marrow in a NOX2/MMP9-dependent Manner and Enhances Neovascularization after Ischemia"],["dc.type","conference_abstract"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","1398"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","Arteriosclerosis, Thrombosis, and Vascular Biology"],["dc.bibliographiccitation.lastpage","U339"],["dc.bibliographiccitation.volume","30"],["dc.contributor.author","Leifheit-Nestler, Maren"],["dc.contributor.author","Conrad, Gaby"],["dc.contributor.author","Heida, Nana-Maria"],["dc.contributor.author","Limbourg, Anne"],["dc.contributor.author","Limbourg, Florian P."],["dc.contributor.author","Seidler, Tim"],["dc.contributor.author","Schroeter, Marco R."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Konstantinides, Stavros"],["dc.contributor.author","Schaefer, Katrin"],["dc.date.accessioned","2017-09-07T11:45:20Z"],["dc.date.available","2017-09-07T11:45:20Z"],["dc.date.issued","2010"],["dc.description.abstract","Objective-To determine the intracellular mechanisms mediating the angiogenic effects of integrin alpha v beta 5 overexpression in circulating angiogenic cells (CACs). Methods and Results-Integrin alpha v beta 5 is expressed on angiogenic endothelial cells, and integrin alpha v beta 5 activation was shown to improve the reparative functions of endothelial progenitors within the cardiovascular system. CACs were transiently transfected with the full-length cDNA of human integrin beta 5 (CAC-ITGB5) or control-vector (CAC-vector). Integrin beta 5 overexpression was confirmed using flow cytometry, Western blot, and PCR analysis; it enhanced the angiogenic capacities of CACs in vitro (spheroid and Matrigel angiogenesis assay) and stimulated new vessel formation in vivo (murine hind limb ischemia model). Overexpression of ITGB5 resulted in integrin alpha v beta 5 phosphorylation and activation of Src kinase and signal transducer and activator of transcription (STAT) 3. Furthermore, elevated mRNA and protein expression of the CXC chemokine CXCL8 and the CC chemokine CCL2 was detected in CAC-ITGB5, and conditioned medium from CAC-ITGB5 enhanced the sprouting of coincubated human endothelial cells in a STAT3-, CXCL8-, and CCL2-dependent manner. Conclusion-Src kinase-mediated activation of STAT3 and subsequent angiogenic gene expression mediate the effects of integrin alpha v beta 5 and may be exploited to enhance the paracrine activities of CACs. (Arterioscler Thromb Vasc Biol. 2010; 30: 1398-1406.)"],["dc.identifier.doi","10.1161/ATVBAHA.110.206086"],["dc.identifier.gro","3142890"],["dc.identifier.isi","000278856600017"],["dc.identifier.pmid","20431064"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/343"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","1079-5642"],["dc.title","Overexpression of Integrin beta 5 Enhances the Paracrine Properties of Circulating Angiogenic Cells via Src Kinase-Mediated Activation of STAT3"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","170"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","180"],["dc.bibliographiccitation.volume","93"],["dc.contributor.author","Schroeter, Marco R."],["dc.contributor.author","Stein, Susanne"],["dc.contributor.author","Heida, Nana-Maria"],["dc.contributor.author","Leifheit-Nestler, Maren"],["dc.contributor.author","Cheng, I-Fen"],["dc.contributor.author","Gogiraju, Rajinikanth"],["dc.contributor.author","Christiansen, Hans"],["dc.contributor.author","Maier, Lars S."],["dc.contributor.author","Shah, Ajay M."],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Konstantinides, Stavros"],["dc.contributor.author","Schaefer, Katrin"],["dc.date.accessioned","2017-09-07T11:43:14Z"],["dc.date.available","2017-09-07T11:43:14Z"],["dc.date.issued","2012"],["dc.description.abstract","Aims Bone marrow (BM) progenitors participate in new vessel formation and endothelial repair. The leptin receptor (ObR) is expressed on hematopoietic cells; however, the effects of leptin on BM progenitor cells and their angiogenic potential are unknown. Methods and results In the present study, we show that the short-term administration of leptin (over five consecutive days) into wild-type mice increased the number of circulating, BM-derived sca-1(+), flk-1(+) vascular progenitors, 95 +/- 1.7% of which also expressed ObR. Ex vivo stimulation of BM cells with leptin enhanced the expression of NADPH oxidase isoform 2 (NOX2), and the leptin-induced increase in reactive oxygen species production, matrix metalloproteinase-9 (MMP9) expression and circulating soluble KitL levels was absent in mice lacking NOX2. Furthermore, intraperitoneal injections of leptin improved perfusion and increased the number of BM-derived, CD31-positive endothelial cells in ischaemic hindlimbs after femoral artery ligation. The effects of leptin on the mobilization of sca-1(+), flk-1(+) cells and neovascularization were abolished in mice transplanted with BM from ObR-deficient and in NOX2(-/-) mice. Conclusion Our findings suggest that the angiogenic effects of leptin involve sca-1(+), flk-1(+) vascular progenitor cells mobilized from the BM in response to ObR-mediated activation of NOX2, increased MMP9 expression, and sKitL release."],["dc.identifier.doi","10.1093/cvr/cvr275"],["dc.identifier.gro","3142608"],["dc.identifier.isi","000298381600022"],["dc.identifier.pmid","22065732"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/31"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0008-6363"],["dc.title","Leptin promotes the mobilization of vascular progenitor cells and neovascularization by NOX2-mediated activation of MMP9"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]