| First Author | Schroeter MR | Year | 2012 |
| Journal | Cardiovasc Res | Volume | 93 |
| Issue | 1 | Pages | 170-80 |
| PubMed ID | 22065732 | Mgi Jnum | J:194875 |
| Mgi Id | MGI:5474932 | Doi | 10.1093/cvr/cvr275 |
| Citation | Schroeter MR, et al. (2012) Leptin promotes the mobilization of vascular progenitor cells and neovascularization by NOX2-mediated activation of MMP9. Cardiovasc Res 93(1):170-80 |
| abstractText | 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. |
