Leptin promotes the mobilization of vascular progenitor cells and neovascularization by NOX2-mediated activation of MMP9
2012 | journal article; research paper. A publication with affiliation to the University of Göttingen.
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Leptin promotes the mobilization of vascular progenitor cells and neovascularization by NOX2-mediated activation of MMP9
Schroeter, M. R. ; Stein, S.; Heida, N.-M.; Leifheit-Nestler, M. ; Cheng, I.-F. ; Gogiraju, R. & Christiansen, H. et al. (2012)
Cardiovascular Research, 93(1) pp. 170-180. DOI: https://doi.org/10.1093/cvr/cvr275
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- Authors
- Schroeter, Marco R. ; Stein, Susanne; Heida, Nana-Maria; Leifheit-Nestler, Maren ; Cheng, I-Fen ; Gogiraju, Rajinikanth; Christiansen, Hans; Maier, Lars S. ; Shah, Ajay M.; Hasenfuß, Gerd ; Konstantinides, Stavros; Schaefer, Katrin
- 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.
- Issue Date
- 2012
- Journal
- Cardiovascular Research
- ISSN
- 0008-6363