TY - JOUR
T1 - PPARγ activation but not PPARγ haplodeficiency affects proangiogenic potential of endothelial cells and bone marrow-derived progenitors
AU - Kotlinowski, Jerzy
AU - Grochot-Przeczek, Anna
AU - Taha, Hevidar
AU - Kozakowska, Magdalena
AU - Pilecki, Bartosz
AU - Skrzypek, Klaudia
AU - Bartelik, Aleksandra
AU - Derlacz, Rafal
AU - Horrevoets, Anton J.G.
AU - Pap, Attila
AU - Nagy, Laszlo
AU - Dulak, Jozef
AU - Jozkowicz, Alicja
N1 - Funding Information:
This work was supported by European Union Framework Program POIG 01.02.00-069/09 and Opus project founded by the National Science Center NCN2012/07/B/NZ1/02881. We used also the equipment obtained from EU Framework Programs POIG 02.01.00-12-064/08, and 02.02.00-00-014/08 (to Faculty of Biochemistry, Biophysics and Biotechnology). A.G-P. was a recipient of L’Oreal Poland for Women in Science Scholarship and START Scholarship of Foundation for Polish Science (FNP). K.S. was a recipient of START Scholarship of FNP. L.N. is supported by a grant from the Hungarian Scientific Research Fund (OTKA K100196).
Publisher Copyright:
© Kotlinowski et al.; licensee BioMed Central Ltd.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Background: Peroxisome proliferator-activated receptor-γ (PPARγ) agonists, which have been used as insulin sensitizers in diabetic patients, may improve functions of endothelial cells (ECs). We investigated the effect of PPARγ on angiogenic activities of murine ECs and bone marrow-derived proangiogenic cells (PACs). Methods: PACs were isolated from bone marrow of 10-12 weeks old, wild type, db/db and PPARγ heterozygous animals. Cells were cultured on fibronectin and gelatin coated dishes in EGM-2MV medium. For in vitro stimulations, rosiglitazone (10 μmol/L) or GW9662 (10 μmol/L) were added to 80% confluent cell cultures for 24 hours. Angiogenic potential of PACs and ECs was tested in vitro and in vivo in wound healing assay and hind limb ischemia model. Results: ECs and PACs isolated from diabetic db/db mice displayed a reduced angiogenic potential in ex vivo and in vitro assays, the effect partially rescued by incubation of cells with rosiglitazone (PPARγ activator). Correction of diabetes by administration of rosiglitazone in vivo did not improve angiogenic potential of isolated PACs or ECs. In a hind limb ischemia model we demonstrated that local injection of conditioned media harvested from wild type PACs improved the blood flow restoration in db/db mice, confirming the importance of paracrine action of the bone marrow-derived cells. Conclusions: In summary, activation of PPARγ by rosiglitazone improves angiogenic potential of diabetic ECs and PACs, but decreased expression of PPARγ in diabetes does not impair angiogenesis.
AB - Background: Peroxisome proliferator-activated receptor-γ (PPARγ) agonists, which have been used as insulin sensitizers in diabetic patients, may improve functions of endothelial cells (ECs). We investigated the effect of PPARγ on angiogenic activities of murine ECs and bone marrow-derived proangiogenic cells (PACs). Methods: PACs were isolated from bone marrow of 10-12 weeks old, wild type, db/db and PPARγ heterozygous animals. Cells were cultured on fibronectin and gelatin coated dishes in EGM-2MV medium. For in vitro stimulations, rosiglitazone (10 μmol/L) or GW9662 (10 μmol/L) were added to 80% confluent cell cultures for 24 hours. Angiogenic potential of PACs and ECs was tested in vitro and in vivo in wound healing assay and hind limb ischemia model. Results: ECs and PACs isolated from diabetic db/db mice displayed a reduced angiogenic potential in ex vivo and in vitro assays, the effect partially rescued by incubation of cells with rosiglitazone (PPARγ activator). Correction of diabetes by administration of rosiglitazone in vivo did not improve angiogenic potential of isolated PACs or ECs. In a hind limb ischemia model we demonstrated that local injection of conditioned media harvested from wild type PACs improved the blood flow restoration in db/db mice, confirming the importance of paracrine action of the bone marrow-derived cells. Conclusions: In summary, activation of PPARγ by rosiglitazone improves angiogenic potential of diabetic ECs and PACs, but decreased expression of PPARγ in diabetes does not impair angiogenesis.
KW - Diabetes
KW - Endothelial progenitor cells
KW - PPARγ
KW - Therapeutic angiogenesis
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U2 - 10.1186/s12933-014-0150-7
DO - 10.1186/s12933-014-0150-7
M3 - Article
C2 - 25361524
AN - SCOPUS:84920847207
SN - 1475-2840
VL - 13
JO - Cardiovascular Diabetology
JF - Cardiovascular Diabetology
IS - 1
M1 - 150
ER -