Leifheit-Nestler, Maren

[["dc.bibliographiccitation.firstpage","357"],["dc.bibliographiccitation.issue","4"],["dc.bibliographiccitation.journal","Journal of the American College of Cardiology"],["dc.bibliographiccitation.lastpage","367"],["dc.bibliographiccitation.volume","55"],["dc.contributor.author","Heida, Nana-Maria"],["dc.contributor.author","Mueller, Jan-Peter"],["dc.contributor.author","Cheng, I-Fen"],["dc.contributor.author","Leifheit-Nestler, Maren"],["dc.contributor.author","Faustin, Vivien"],["dc.contributor.author","Riggert, Joachim"],["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","Objectives The purpose of this study was to examine the impact of obesity and weight loss on the angiogenic and regenerative capacity of endothelial progenitor cells (EPCs). Background EPCs participate in angiogenesis and tissue repair. Several cardiovascular risk factors are associated with EPC dysfunction. Methods Early outgrowth EPCs were isolated from 49 obese (age 42 +/- 14 years; body mass index 42 +/- 7 kg/m(2)) normo-glycemic participants in a professional weight reduction program and compared with those from 49 age-matched lean controls. EPC function was tested both in vitro and in vivo. Results EPCs expanded from the obese possessed reduced adhesive, migratory, and angiogenic capacity, and mice treated with obese EPCs exhibited reduced EPC homing in ischemic hind limbs in vivo. EPCs from the obese subjects failed to respond to conditioned medium of lean controls or to potent angiogenic factors such as vascular endothelial growth factor. Although no differences existed between lean and obese EPCs regarding the surface expression of vascular endothelial growth factor or chemokine receptors, basal p38 mitogen-activated protein kinase (MAPK) phosphorylation was elevated in obese EPCs (3.7 +/- 2.1-fold increase; p = 0.006). These cells also showed reduced secretion of the angiogenic chemokines interleukin-8 (p = 0.047) and monocyte chemoattractant protein-1 (p = 0.012). By inhibiting p38 MAPK, we could restore chemokine levels to those of lean control EPCs and also improve the angiogenic properties of obese EPCs. Accordingly, 6-month follow-up of 26 obese persons who achieved significant weight reduction revealed normalization of p38 MAPK phosphorylation levels and improved EPC function. Conclusions Obesity is associated with a reversible functional impairment of EPCs. This involves reduced secretion of angiogenic chemokines and increased basal phosphorylation of signaling molecules, notably p38 MAPK. (J Am Coll Cardiol 2010; 55: 357-67) (C) 2010 by the American College of Cardiology Foundation"],["dc.identifier.doi","10.1016/j.jacc.2009.09.031"],["dc.identifier.gro","3142979"],["dc.identifier.isi","000273802200013"],["dc.identifier.pmid","20117442"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/6292"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/442"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Elsevier Science Inc"],["dc.relation.issn","0735-1097"],["dc.rights","Goescholar"],["dc.rights.uri","https://goescholar.uni-goettingen.de/licenses"],["dc.title","Effects of Obesity and Weight Loss on the Functional Properties of Early Outgrowth Endothelial Progenitor Cells"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dspace.entity.type","Publication"]]

[["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.firstpage","13"],["dc.bibliographiccitation.issue","1"],["dc.bibliographiccitation.journal","Neuropsychobiology"],["dc.bibliographiccitation.lastpage","22"],["dc.bibliographiccitation.volume","77"],["dc.contributor.author","Kranaster, Laura"],["dc.contributor.author","Hoyer, Carolin"],["dc.contributor.author","Aksay, Suna S."],["dc.contributor.author","Bumb, J. Malte"],["dc.contributor.author","Müller, Norbert"],["dc.contributor.author","Zill, Peter"],["dc.contributor.author","Schwarz, Markus J."],["dc.contributor.author","Moll, Natalie"],["dc.contributor.author","Lutz, Beat"],["dc.contributor.author","Bindila, Laura"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Blennow, Kaj"],["dc.contributor.author","Zetterberg, Henrik"],["dc.contributor.author","Haffner, Dieter"],["dc.contributor.author","Leifheit-Nestler, Maren"],["dc.contributor.author","Ozbalci, Cagakan"],["dc.contributor.author","Janke, Christoph"],["dc.contributor.author","Thiel, Manfred"],["dc.contributor.author","Sartorius, Alexander"],["dc.date.accessioned","2020-12-10T18:37:51Z"],["dc.date.available","2020-12-10T18:37:51Z"],["dc.date.issued","2018"],["dc.identifier.doi","10.1159/000491401"],["dc.identifier.eissn","1423-0224"],["dc.identifier.issn","0302-282X"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/77111"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","Biomarkers for Antidepressant Efficacy of Electroconvulsive Therapy: An Exploratory Cerebrospinal Fluid Study"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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.artnumber","170"],["dc.bibliographiccitation.journal","Journal of Translational Medicine"],["dc.bibliographiccitation.volume","11"],["dc.contributor.author","Leifheit-Nestler, Maren"],["dc.contributor.author","Wagner, Nana-Maria"],["dc.contributor.author","Gogiraju, Rajinikanth"],["dc.contributor.author","Didie, Michael"],["dc.contributor.author","Konstantinides, Stavros"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Schaefer, Katrin"],["dc.date.accessioned","2017-09-07T11:47:39Z"],["dc.date.available","2017-09-07T11:47:39Z"],["dc.date.issued","2013"],["dc.description.abstract","Background: The adipokine leptin and its receptor are expressed in the heart, and leptin has been shown to promote cardiomyocyte hypertrophy in vitro. Obesity is associated with hyperleptinemia and hypothalamic leptin resistance as well as an increased risk to develop cardiac hypertrophy and heart failure. However, the role of cardiac leptin signaling in mediating the cardiomyopathy associated with increased body weight is unclear, in particular, whether it develops subsequently to cardiac leptin resistance or overactivation of hypertrophic signaling pathways via elevated leptin levels. Methods: The cardiac phenotype of high-fat diet (HFD)-induced obese wildtype (WT) mice was examined and compared to age-matched genetically obese leptin receptor (LepR)-deficient (LepR(db/db)) or lean WT mice. To study the role of leptin-mediated STAT3 activation during obesity-induced cardiac remodeling, mice in which tyrosine residue 1138 within LepR had been replaced with a serine (LepR(S1138)) were also analyzed. Results: Obesity was associated with hyperleptinemia and elevated cardiac leptin expression in both diet-induced and genetically obese mice. Enhanced LepR and STAT3 phosphorylation levels were detected in hearts of obese WT mice, but not in those with LepR mutations. Moreover, exogenous leptin continued to induce cardiac STAT3 activation in diet-induced obese mice. Although echocardiography revealed signs of cardiac hypertrophy in all obese mice, the increase in left ventricular (LV) mass and diameter was significantly more pronounced in LepR(S1138) animals. LepR(S1138) mice also exhibited an increased activation of signaling proteins downstream of LepR, including Jak2 (1.8-fold), Src kinase (1.7-fold), protein kinase B (1.3-fold) or C (1.6-fold). Histological analysis of hearts revealed that the inability of leptin to activate STAT3 in LepR(db/db) and LepR(S1138) mice was associated with reduced cardiac angiogenesis as well as increased apoptosis and fibrosis. Conclusions: Our findings suggest that hearts from obese mice continue to respond to elevated circulating or cardiac leptin, which may mediate cardioprotection via LepR-induced STAT3 activation, whereas signals distinct from LepR-Tyr1138 promote cardiac hypertrophy. On the other hand, the presence of cardiac hypertrophy in obese mice with complete LepR signal disruption indicates that additional pathways also play a role."],["dc.identifier.doi","10.1186/1479-5876-11-170"],["dc.identifier.gro","3142325"],["dc.identifier.isi","000321925200001"],["dc.identifier.pmid","23841921"],["dc.identifier.purl","https://resolver.sub.uni-goettingen.de/purl?gs-1/9149"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/7031"],["dc.notes.intern","WoS Import 2017-03-10"],["dc.notes.intern","Merged from goescholar"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.publisher","Biomed Central Ltd"],["dc.relation.issn","1479-5876"],["dc.rights","CC BY 2.0"],["dc.rights.uri","https://creativecommons.org/licenses/by/2.0"],["dc.title","Importance of leptin signaling and signal transducer and activator of transcription-3 activation in mediating the cardiac hypertrophy associated with obesity"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["dc.type.version","published_version"],["dspace.entity.type","Publication"]]

[["dc.bibliographiccitation.firstpage","555"],["dc.bibliographiccitation.issue","3"],["dc.bibliographiccitation.journal","Cardiovascular Research"],["dc.bibliographiccitation.lastpage","565"],["dc.bibliographiccitation.volume","99"],["dc.contributor.author","Schroeter, Marco R."],["dc.contributor.author","Leifheit-Nestler, Maren"],["dc.contributor.author","Hubert, Astrid"],["dc.contributor.author","Schumann, Bettina"],["dc.contributor.author","Glueckermann, Roland"],["dc.contributor.author","Eschholz, Norman"],["dc.contributor.author","Krueger, Nenja"],["dc.contributor.author","Lutz, Susanne"],["dc.contributor.author","Hasenfuß, Gerd"],["dc.contributor.author","Konstantinides, Stavros"],["dc.contributor.author","Schaefer, Katrin"],["dc.date.accessioned","2017-09-07T11:47:38Z"],["dc.date.available","2017-09-07T11:47:38Z"],["dc.date.issued","2013"],["dc.description.abstract","Apolipoprotein E (apoE) may act as a vasculoprotective factor by promoting plasma lipid clearance and cholesterol efflux. Moreover, apoE accumulates at sites of vascular injury and modulates the effect of growth factors on smooth muscle cells (SMCs). Experimental data suggested that hypothalamic apoE expression is reduced in obesity and associated with leptin resistance. In this study, we examined the role of apoE in mediating the effects of leptin on vascular lesion formation. Leptin was administered to apoE knockout (apoE(/)) mice via osmotic pumps to increase its circulating levels. Morphometric analysis revealed that leptin did not alter neointima formation and failed to increase -actin- or PCNA-immunopositive SMCs after vascular injury. Similar findings were obtained after analysis of atherosclerotic lesions. Comparison of apoE(/), wild-type, or LDL receptor(/) mice and functional analyses in aortic SMCs from WT or apoE(/) mice or human arterial SMCs after treatment with small interfering (si)RNA or heparinase revealed that leptin requires the presence of apoE, expressed, secreted and bound to the cell surface, to fully activate leptin receptor signalling and to promote SMC proliferation and neointima formation. Mechanistically, leptin induced the phosphorylation and membrane translocation of caveolin (cav)-1, and apoE down-regulation or caveolae disruption inhibited the leptin-induced p47(phox) activation, ROS formation and SMC proliferation. Finally, leptin failed to increase neointima formation in mice lacking cav-1. Our findings suggest that apoE mediates the effects of leptin on vascular lesion formation by stabilizing cav-1-enriched cell membrane microdomains in SMCs, thus allowing NADPH oxidase assembly and ROS-mediated mitogenic signalling."],["dc.identifier.doi","10.1093/cvr/cvt126"],["dc.identifier.gro","3142315"],["dc.identifier.isi","000322341600021"],["dc.identifier.pmid","23723060"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/6920"],["dc.notes.intern","WoS Import 2017-03-10 / Funder: German Research Foundation; Novartis Foundation for Therapeutic Research"],["dc.notes.status","final"],["dc.notes.submitter","PUB_WoS_Import"],["dc.relation.issn","0008-6363"],["dc.title","Leptin promotes neointima formation and smooth muscle cell proliferation via NADPH oxidase activation and signalling in caveolin-rich microdomains"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.subtype","original"],["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","911"],["dc.bibliographiccitation.issue","7"],["dc.bibliographiccitation.journal","European Archives of Psychiatry and Clinical Neuroscience"],["dc.bibliographiccitation.lastpage","919"],["dc.bibliographiccitation.volume","270"],["dc.contributor.author","Kranaster, Laura"],["dc.contributor.author","Hoyer, Carolin"],["dc.contributor.author","Mindt, Sonani"],["dc.contributor.author","Neumaier, Michael"],["dc.contributor.author","Müller, Norbert"],["dc.contributor.author","Zill, Peter"],["dc.contributor.author","Schwarz, Markus J."],["dc.contributor.author","Moll, Natalie"],["dc.contributor.author","Lutz, Beat"],["dc.contributor.author","Bindila, Laura"],["dc.contributor.author","Zerr, Inga"],["dc.contributor.author","Schmitz, Matthias"],["dc.contributor.author","Blennow, Kaj"],["dc.contributor.author","Zetterberg, Henrik"],["dc.contributor.author","Haffner, Dieter"],["dc.contributor.author","Leifheit-Nestler, Maren"],["dc.contributor.author","Ozbalci, Cagakan"],["dc.contributor.author","Sartorius, Alexander"],["dc.date.accessioned","2020-12-10T14:10:32Z"],["dc.date.available","2020-12-10T14:10:32Z"],["dc.date.issued","2019"],["dc.identifier.doi","10.1007/s00406-019-01086-x"],["dc.identifier.eissn","1433-8491"],["dc.identifier.issn","0940-1334"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/70789"],["dc.language.iso","en"],["dc.notes.intern","DOI Import GROB-354"],["dc.title","The novel seizure quality index for the antidepressant outcome prediction in electroconvulsive therapy: association with biomarkers in the cerebrospinal fluid"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["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"]]

[["dc.bibliographiccitation.firstpage","980"],["dc.bibliographiccitation.issue","5"],["dc.bibliographiccitation.journal","Arteriosclerosis Thrombosis and Vascular Biology"],["dc.bibliographiccitation.lastpage","U279"],["dc.bibliographiccitation.volume","33"],["dc.contributor.author","Schroeter, M. R."],["dc.contributor.author","Eschholz, Norman"],["dc.contributor.author","Herzberg, Sebastian"],["dc.contributor.author","Jerchel, Isabel"],["dc.contributor.author","Leifheit-Nestler, Maren"],["dc.contributor.author","Czepluch, Frauke S."],["dc.contributor.author","Chalikias, Georgios"],["dc.contributor.author","Konstantinides, Stavros V."],["dc.contributor.author","Schaefer, Katrin"],["dc.date.accessioned","2018-11-07T09:25:35Z"],["dc.date.available","2018-11-07T09:25:35Z"],["dc.date.issued","2013"],["dc.description.abstract","Objective-Clinical and experimental evidence suggests that periadventitial adipose tissue may modulate vascular lesion formation. The aim of this study was to determine the role of perivascular leptin expression on neointima formation and to differentiate it from local inflammation and systemically elevated leptin levels. Approach and Results-Increased neointima formation after carotid artery injury was observed in hyperleptinemic, diet-induced obese wild-type mice, but not in leptin-deficient ob/ob mice. High-fat diet was associated with increased leptin expression in visceral adipose tissue (VAT) as well as in perivascular adipose tissue. Perivascular leptin overexpression achieved by adenoviral vectors enhanced intimal cell proliferation and neointima formation in wild-type mice, but not in leptin receptor-deficient mice. Perivascular transplantation of VAT from high-fat diet-induced obese wild-type mice around the carotid artery of immunodeficient mice also promoted neointima formation, without affecting body weight or systemic leptin levels, and this effect was absent, if VAT from ob/ob mice was used. On the contrary, perivascular transplantation of VAT from ob/ob mice fed high-fat diet, characterized by marked immune cell accumulation, promoted neointimal hyperplasia also in the absence of leptin. In vitro, recombinant leptin and VAT-conditioned medium increased human arterial smooth muscle cell proliferation in a (partly) leptin-dependent manner. Conclusions-Our findings suggest that locally elevated leptin levels may promote neointima formation, independent of obesity and systemic hyperleptinemia, but also underline the importance of perivascular inflammation in mediating the increased cardiovascular risk in obesity. (Arterioscler Thromb Vasc Biol. 2013; 33: 980-987.)"],["dc.identifier.doi","10.1161/ATVBAHA.113.301393"],["dc.identifier.isi","000317476000019"],["dc.identifier.pmid","23520165"],["dc.identifier.uri","https://resolver.sub.uni-goettingen.de/purl?gro-2/30097"],["dc.notes.status","zu prüfen"],["dc.notes.submitter","Najko"],["dc.publisher","Lippincott Williams & Wilkins"],["dc.relation.issn","1079-5642"],["dc.title","Leptin-Dependent and Leptin-Independent Paracrine Effects of Perivascular Adipose Tissue on Neointima Formation"],["dc.type","journal_article"],["dc.type.internalPublication","yes"],["dc.type.peerReviewed","yes"],["dc.type.status","published"],["dspace.entity.type","Publication"]]