ActionsCite Favorites Display options Display options Format Obese diabetic mouse environment differentially affects primitive and monocytic endothelial cell progenitors Obese diabetic mouse environment differentially affects primitive and monocytic endothelial cell progenitors Two classes of adult bone marrow-derived endothelial cell (EC) progenitors have been described, primitive hematopoietic stem cell-related cells and monocytic cells. Both differentiate into ECs and promote vascular growth in vivo but have distinct characteristics. Despite the association of obesity and type 2 diabetes with cardiovascular disease, their effects on primitive EC progenitors (prECPs) have not been examined, and the limited data on monocytic EC progenitors are conflicting. We investigated functional parameters of primitive and monocytic EC progenitors from obese diabetic (Lepr(db)) mice. The viability, proliferation, and differentiation of EC progenitors were unaffected in Lepr(db) cell cultures under basal condition. However, Lepr(db)-derived prECPs, but not monocytic EC progenitors, were less able to cope with hypoxia and oxidative stress, conditions likely present when EC progenitors are most needed. Intrinsic prECP dysfunction was also apparent in vivo. Whereas injection of nondiabetic prECPs promoted vascularization of skin wounds, Lepr(db)-derived progenitors inhibited it in nondiabetic mice. Additionally, although treatment with Lepr(db)-derived prECPs did not significantly reduce blood flow restoration to ischemic limbs, it resulted in increased tissue necrosis and autoamputation. Thus, type 2 diabetes coupled with obesity seems to induce intrinsic EC progenitor dysfunction that is exacerbated by stress. prECPs are more affected than monocytic progenitors, exhibiting a reduced ability to survive or proliferate. The proangiogenic phenotype of prECPs also seems to convert to an antiangiogenic phenotype in obese diabetic mice. These data suggest that therapies involving prECPs or stem-like cells in diabetic patients may be inadvisable at this time. Stepanovic V, et al. Circ Res. 2003 Jun 13;92(11):1247-53. doi: 10.1161/01.RES.0000074906.98021.55. Epub 2003 May 1. Circ Res. 2003. PMID: 12730094 Awad O, et al. Arterioscler Thromb Vasc Biol. 2006 Apr;26(4):758-64. doi: 10.1161/01.ATV.0000203513.29227.6f. Epub 2006 Jan 12. Arterioscler Thromb Vasc Biol. 2006. PMID: 16410458 Schatteman GC, et al. Stem Cells. 2006 Mar;24(3):717-21. doi: 10.1634/stemcells.2005-0214. Epub 2005 Nov 3. Stem Cells. 2006. PMID: 16269529 Schatteman GC, et al. Anat Rec A Discov Mol Cell Evol Biol. 2004 Jan;276(1):13-21. doi: 10.1002/ar.a.10131. Anat Rec A Discov Mol Cell Evol Biol. 2004. PMID: 14699630 Kim JS, Jung YH, Lee HJ, Chae CW, Choi GE, Lim JR, Kim SY, Lee JE, Han HJ. Kim JS, et al. Stem Cell Res Ther. 2021 Feb 5;12(1):114. doi: 10.1186/s13287-021-02181-4. Stem Cell Res Ther. 2021. PMID: 33546749 Free PMC article. Jarajapu YPR. Mol Pharmacol. 2021 Jan;99(1):29-38. doi: 10.1124/mol.119.117580. Epub 2020 Apr 22. Mol Pharmacol. 2021. PMID: 32321734 BMC Vet Res. 2018 Aug 23;14(1):247. doi: 10.1186/s12917-018-1572-3. BMC Vet Res. 2018. PMID: 30139355 Free PMC article. Irhimeh MR, Hamed M, Barthelmes D, Gladbach Y, Helms V, Shen W, Gillies MC. Irhimeh MR, et al. PLoS One. 2018 Jul 11;13(7):e0200194. doi: 10.1371/journal.pone.0200194. eCollection 2018. PLoS One. 2018. PMID: 29995913 Free PMC article. Chambers SEJ, O\'Neill CL, Guduric-Fuchs J, McLoughlin KJ, Liew A, Egan AM, O\'Brien T, Stitt AW, Medina RJ. Chambers SEJ, et al. Stem Cells. 2018 Jun;36(6):834-843. doi: 10.1002/stem.2810. Epub 2018 Mar 9. Stem Cells. 2018. PMID: 29484768 Free PMC article.