PPARγ activation but not PPARγ haplodeficiency affects proangiogenic potential of endothelial cells and bone marrow-derived progenitors

Jerzy Kotlinowski, Anna Grochot-Przeczek, Hevidar Taha, Magdalena Kozakowska, Bartosz Pilecki, Klaudia Skrzypek, Aleksandra Bartelik, Rafal Derlacz, Anton J G Horrevoets, Attila Pap, L. Nagy, Jozef Dulak, Alicja Jozkowicz

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish
Article number150
JournalCardiovascular Diabetology
Volume13
Issue number1
DOIs
Publication statusPublished - Nov 1 2014

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rosiglitazone
Peroxisome Proliferator-Activated Receptors
Endothelial Cells
Bone Marrow
Ischemia
Extremities
Gelatin
Conditioned Culture Medium
Fibronectins
Bone Marrow Cells
Wound Healing
Cultured Cells
Blood Cells
Cell Culture Techniques
Insulin
Injections

Keywords

  • Diabetes
  • Endothelial progenitor cells
  • PPARγ
  • Therapeutic angiogenesis

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Kotlinowski, J., Grochot-Przeczek, A., Taha, H., Kozakowska, M., Pilecki, B., Skrzypek, K., ... Jozkowicz, A. (2014). PPARγ activation but not PPARγ haplodeficiency affects proangiogenic potential of endothelial cells and bone marrow-derived progenitors. Cardiovascular Diabetology, 13(1), [150]. https://doi.org/10.1186/s12933-014-0150-7

PPARγ activation but not PPARγ haplodeficiency affects proangiogenic potential of endothelial cells and bone marrow-derived progenitors. / Kotlinowski, Jerzy; Grochot-Przeczek, Anna; Taha, Hevidar; Kozakowska, Magdalena; Pilecki, Bartosz; Skrzypek, Klaudia; Bartelik, Aleksandra; Derlacz, Rafal; Horrevoets, Anton J G; Pap, Attila; Nagy, L.; Dulak, Jozef; Jozkowicz, Alicja.

In: Cardiovascular Diabetology, Vol. 13, No. 1, 150, 01.11.2014.

Research output: Contribution to journalArticle

Kotlinowski, J, Grochot-Przeczek, A, Taha, H, Kozakowska, M, Pilecki, B, Skrzypek, K, Bartelik, A, Derlacz, R, Horrevoets, AJG, Pap, A, Nagy, L, Dulak, J & Jozkowicz, A 2014, 'PPARγ activation but not PPARγ haplodeficiency affects proangiogenic potential of endothelial cells and bone marrow-derived progenitors', Cardiovascular Diabetology, vol. 13, no. 1, 150. https://doi.org/10.1186/s12933-014-0150-7
Kotlinowski, Jerzy ; Grochot-Przeczek, Anna ; Taha, Hevidar ; Kozakowska, Magdalena ; Pilecki, Bartosz ; Skrzypek, Klaudia ; Bartelik, Aleksandra ; Derlacz, Rafal ; Horrevoets, Anton J G ; Pap, Attila ; Nagy, L. ; Dulak, Jozef ; Jozkowicz, Alicja. / PPARγ activation but not PPARγ haplodeficiency affects proangiogenic potential of endothelial cells and bone marrow-derived progenitors. In: Cardiovascular Diabetology. 2014 ; Vol. 13, No. 1.
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abstract = "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.",
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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, L.

AU - Dulak, Jozef

AU - Jozkowicz, Alicja

PY - 2014/11/1

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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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