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.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"]]