期刊
NEPHROLOGY DIALYSIS TRANSPLANTATION
卷 27, 期 1, 页码 218-225出版社
OXFORD UNIV PRESS
DOI: 10.1093/ndt/gfr267
关键词
angiogenesis; bone marrow-derived stromal cells; cardiovascular disease; chronic kidney disease
资金
- Ministry for Health, Welfare & Family Affairs, Republic of Korea [A090295]
- National Research Foundation of Korea
- Korean Government [2009-0072323]
- Korea Health Promotion Institute [A090295] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
- National Research Foundation of Korea [2009-0072323] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Background. Chronic kidney disease (CKD) is associated with increased risk for cardiovascular diseases (CVD). We hypothesized that inadequate angiogenic response in uremic patients could result from dysfunction of bone marrow-derived stromal cells [mesenchymal stem cells (MSCs)]. Methods. We investigated whether MSCs are functionally competent in uremia induced by partial kidney ablation in C57Bl/6J mice. Results. Uremic MSCs showed decreased expression of vascular endothelial growth factor (VEGF), VEGF receptor (VEGFR) 1 and stromal cell-derived factor (SDF)-1 alpha, increased cellular senescence, decreased proliferation, defects in migration in response to VEGF and SDF-1 alpha and in vitro tube formation. Interestingly, the expression of fibroblast-specific protein-1 was higher in uremic MSCs. Uremia decreased hypoxia-inducible factor-1 alpha, VEGF and VEGFR1 expression under hypoxia and Akt phosphorylation in both basal and VEGF-stimulated states. A diminished mitogenic effect on endothelial proliferation was observed in conditioned media from uremic MSCs. In addition, intravital microscopic analysis showed decreased angiogenesis in uremic MSCs. Conclusion. These results clearly demonstrate the functional incompetence in MSCs under uremic conditions and may significantly contribute to the disproportionately high risk for CVD in patients with CKD.
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