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Paracrine Dysfunction in Diabetic Endothelial Progenitor Cells
Author(s) -
Jarajapu Yagna PR,
Raizada Mohan K,
Bartelmez Stephen H,
Grant Maria B
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.631.10
We tested the hypothesis that endothelial progenitor cells (EPCs) of diabetic (DM) origin have impaired paracrine signaling. Circulating lin − CD45 mid CD34 + cells from DM and nondiabetic (ND) individuals were studied. EPCs were plated in basal medium (18–20 hours) and the conditioned‐medium (CM) was concentrated and analyzed for cytokines and growth factors. The effects of CM were assessed on migration and proliferation of ND‐derived EPCs and in the wire‐mounted mouse mesenteric arteries (MMAs). Paracrine vascular effects of intraluminal EPCs were assessed in pressurized rat posterior cerebral arteries (RPCAs). TNFα, MCP1, IL‐1, IL‐6, IL‐8 and TGFβ1 levels were higher and SCF, HGF and decorin levels were lower in CM from DM‐EPCs compared to ND‐EPCs. CM from both DM‐ and ND‐EPCs increased migration of ND‐EPCs but their proliferation was supported by only CM from ND‐EPCs. In the presence of CM from ND‐EPCs, bradykinin (BK)‐induced relaxation was increased and the sensitivity to phenylephrine (PE)‐induced constriction was decreased. In contrast, in the presence of CM from DM‐EPCs BK‐induced dilation was not affected but the sensitivity to PE‐constriction was enhanced. Intraluminal ND‐EPCs significantly decreased pressure‐induced constriction in RPCAs. In contrast, EPCs had no effect. These results suggest that diabetic vasoreparative dysfunction in EPCs is associated with impaired paracrine function.