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PPAR\gamma activation but not PPAR\gamma haplodeficiency affects proangiogenic potential of endothelial cells and bone marrow-derived progenitors
diabetes
PPARγ
therapeutic angiogenesis
endothelial progenitor cells
Background. Peroxisome proliferator-activated receptor-? (PPAR?) agonists, which have been used as insulin sensitizers in diabetic patients, may improve functions of endothelial cells (ECs). We investigated the effect of PPAR? 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 PPAR? heterozygous animals. Cells were cultured on fibronectin and gelatin coated dishes in EGM-2MV medium. For in vitro stimulations, rosiglitazone (10 ?mol/L) or GW9662 (10 ?mol/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 (PPAR? 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. Transcriptome analysis showed an upregulation of prooxidative and proinflammatory pathways, and downregulation of several proangiogenic genes in db/db PACs. Interestingly, db/db PACs had also a decreased level of PPAR? and changed expression of PPAR?-regulated genes. Using normoglycemic PPAR?+/? mice we demonstrated that reduced expression of PPAR? does not influence neovascularization either in wound healing or in hind limb ischemia models. Conclusions. In summary, activation of PPAR? by rosiglitazone improves angiogenic potential of diabetic ECs and PACs, but decreased expression of PPAR? in diabetes does not impair angiogenesis.
dc.abstract.en | Background. Peroxisome proliferator-activated receptor-? (PPAR?) agonists, which have been used as insulin sensitizers in diabetic patients, may improve functions of endothelial cells (ECs). We investigated the effect of PPAR? 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 PPAR? heterozygous animals. Cells were cultured on fibronectin and gelatin coated dishes in EGM-2MV medium. For in vitro stimulations, rosiglitazone (10 ?mol/L) or GW9662 (10 ?mol/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 (PPAR? 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. Transcriptome analysis showed an upregulation of prooxidative and proinflammatory pathways, and downregulation of several proangiogenic genes in db/db PACs. Interestingly, db/db PACs had also a decreased level of PPAR? and changed expression of PPAR?-regulated genes. Using normoglycemic PPAR?+/? mice we demonstrated that reduced expression of PPAR? does not influence neovascularization either in wound healing or in hind limb ischemia models. Conclusions. In summary, activation of PPAR? by rosiglitazone improves angiogenic potential of diabetic ECs and PACs, but decreased expression of PPAR? in diabetes does not impair angiogenesis. | pl |
dc.affiliation | Wydział Biochemii, Biofizyki i Biotechnologii : Zakład Biotechnologii Medycznej | pl |
dc.contributor.author | Kotlinowski, Jerzy - 135794 | pl |
dc.contributor.author | Grochot-Przęczek, Anna - 173353 | pl |
dc.contributor.author | Taha, Hevidar | pl |
dc.contributor.author | Kozakowska, Magdalena - 135802 | pl |
dc.contributor.author | Pilecki, Bartosz | pl |
dc.contributor.author | Skrzypek, Klaudia - 103991 | pl |
dc.contributor.author | Zimoch, Jakub | pl |
dc.contributor.author | Bartelik, Aleksandra | pl |
dc.contributor.author | Derlacz, Rafał | pl |
dc.contributor.author | Horrevoets, Anton J. G. | pl |
dc.contributor.author | Pap, Attila | pl |
dc.contributor.author | Nagy, Laszlo | pl |
dc.contributor.author | Dulak, Józef - 127818 | pl |
dc.contributor.author | Józkowicz, Alicja - 128541 | pl |
dc.date.accessioned | 2015-05-18T09:20:36Z | |
dc.date.available | 2015-05-18T09:20:36Z | |
dc.date.issued | 2014 | pl |
dc.date.openaccess | 0 | |
dc.description.accesstime | w momencie opublikowania | |
dc.description.additional | Bibliogr. s. 17-19; Erratum: Cardiovascular Diabetology, 2015, vol. 14, p. 65, DOI: 10.1186/s12933-015-0205-4 | pl |
dc.description.admin | [AB] Taha, Hevidar 50000142 | |
dc.description.admin | [AB] Skrzypek, Klaudia 50000142 | |
dc.description.admin | [AB] Pilecki, Bartosz 50000142 | |
dc.description.admin | [AB] Zimoch, Jakub 50000142 | |
dc.description.version | ostateczna wersja wydawcy | |
dc.description.volume | 13 | pl |
dc.identifier.articleid | 150 | pl |
dc.identifier.doi | 10.1186/s12933-014-0150-7 | pl |
dc.identifier.eissn | 1475-2840 | pl |
dc.identifier.project | ROD UJ / P | pl |
dc.identifier.uri | http://ruj.uj.edu.pl/xmlui/handle/item/7265 | |
dc.language | eng | pl |
dc.language.container | eng | pl |
dc.rights | Udzielam licencji. Uznanie autorstwa 4.0 Międzynarodowa | * |
dc.rights.licence | CC-BY | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/legalcode.pl | * |
dc.share.type | otwarte czasopismo | |
dc.subject.en | diabetes | pl |
dc.subject.en | PPARγ | pl |
dc.subject.en | therapeutic angiogenesis | pl |
dc.subject.en | endothelial progenitor cells | pl |
dc.subtype | Article | pl |
dc.title | PPAR\gamma activation but not PPAR\gamma haplodeficiency affects proangiogenic potential of endothelial cells and bone marrow-derived progenitors | pl |
dc.title.journal | Cardiovascular Diabetology | pl |
dc.type | JournalArticle | pl |
dspace.entity.type | Publication |
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