Activation of PPARbeta/delta Induces Endothelial Cell Proliferation and Angiogenesis Export

@article{citeulike:2742061, abstract = {Objective-- The role of the nuclear receptor peroxisome-proliferator activated receptor (PPAR)-{beta}/{delta} in endothelial cells remains unclear. Interestingly, the selective PPAR{beta}/{delta} ligand GW501516 is in phase II clinical trials for dyslipidemia. Here, using GW501516, we have assessed the involvement of PPAR{beta}/{delta} in endothelial cell proliferation and angiogenesis. Methods and Results-- Western blot analysis indicated PPAR{beta}/{delta} was expressed in primary human umbilical and aortic endothelial cells, and in the endothelial cell line, EAHy926. Treatment with GW501516 increased human endothelial cell proliferation and morphogenesis in cultures in vitro, endothelial cell outgrowth from murine aortic vessels in vitro, and angiogenesis in a murine matrigel plug assay in vivo. GW501516 induced vascular endothelial cell growth factor mRNA and peptide release, as well as adipose differentiation-related protein (ADRP), a PPAR{beta}/{delta} target gene. GW501516-induced proliferation, morphogenesis, vascular endothelial growth factor (VEGF), and ADRP were absent in endothelial cells transfected with dominant-negative PPAR{beta}/{delta}. Furthermore, treatment of cells with cyclo-VEGFI, a VEGF receptor1/2 antagonist, abolished GW501516-induced endothelial cell proliferation and tube formation. Conclusions-- PPAR{beta}/{delta} is a novel regulator of endothelial cell proliferation and angiogenesis through VEGF. The use of GW501516 to treat dyslipidemia may need to be carefully monitored in patients susceptible to angiogenic disorders. PPAR{beta}/{delta} is expressed in vascular endothelial cells; however, its roles remain unclear. The PPAR{beta}/{delta} ligand GW501516 induced endothelial proliferation and angiogenesis. The clinical use of GW501516 in dyslipidemia may therefore need to be monitored for angiogenic processes. 10.1161/01.ATV.0000250972.83623.61}, author = {Piqueras, Laura and Reynolds, Andrew R. and Hodivala-Dilke, Kairbaan M. and Alfranca, Arantzazu and Redondo, Juan M. and Hatae, Toshihisa and Tanabe, Tadashi and Warner, Timothy D. and Bishop-Bailey, David}, citeulike-article-id = {2742061}, citeulike-linkout-0 = {http://dx.doi.org/10.1161/01.ATV.0000250972.83623.61}, citeulike-linkout-1 = {http://atvb.ahajournals.org/cgi/content/abstract/27/1/63}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/17068288}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=17068288}, day = {1}, doi = {10.1161/01.ATV.0000250972.83623.61}, journal = {Arterioscler Thromb Vasc Biol}, keywords = {angiogenesis, aorta}, month = {January}, number = {1}, pages = {63--69}, posted-at = {2008-05-01 09:21:30}, priority = {2}, title = {Activation of PPAR{beta}/{delta} Induces Endothelial Cell Proliferation and Angiogenesis}, url = {http://dx.doi.org/10.1161/01.ATV.0000250972.83623.61}, volume = {27}, year = {2007} }

TY - JOUR ID - citeulike:2742061 L3 - citeulike-article-id:2742061 N2 - Objective-- The role of the nuclear receptor peroxisome-proliferator activated receptor (PPAR)-{beta}/{delta} in endothelial cells remains unclear. Interestingly, the selective PPAR{beta}/{delta} ligand GW501516 is in phase II clinical trials for dyslipidemia. Here, using GW501516, we have assessed the involvement of PPAR{beta}/{delta} in endothelial cell proliferation and angiogenesis. Methods and Results-- Western blot analysis indicated PPAR{beta}/{delta} was expressed in primary human umbilical and aortic endothelial cells, and in the endothelial cell line, EAHy926. Treatment with GW501516 increased human endothelial cell proliferation and morphogenesis in cultures in vitro, endothelial cell outgrowth from murine aortic vessels in vitro, and angiogenesis in a murine matrigel plug assay in vivo. GW501516 induced vascular endothelial cell growth factor mRNA and peptide release, as well as adipose differentiation-related protein (ADRP), a PPAR{beta}/{delta} target gene. GW501516-induced proliferation, morphogenesis, vascular endothelial growth factor (VEGF), and ADRP were absent in endothelial cells transfected with dominant-negative PPAR{beta}/{delta}. Furthermore, treatment of cells with cyclo-VEGFI, a VEGF receptor1/2 antagonist, abolished GW501516-induced endothelial cell proliferation and tube formation. Conclusions-- PPAR{beta}/{delta} is a novel regulator of endothelial cell proliferation and angiogenesis through VEGF. The use of GW501516 to treat dyslipidemia may need to be carefully monitored in patients susceptible to angiogenic disorders. PPAR{beta}/{delta} is expressed in vascular endothelial cells; however, its roles remain unclear. The PPAR{beta}/{delta} ligand GW501516 induced endothelial proliferation and angiogenesis. The clinical use of GW501516 in dyslipidemia may therefore need to be monitored for angiogenic processes. 10.1161/01.ATV.0000250972.83623.61 IS - 1 JF - Arterioscler Thromb Vasc Biol EP - 69 TI - Activation of PPAR{beta}/{delta} Induces Endothelial Cell Proliferation and Angiogenesis VL - 27 SP - 63 KW - angiogenesis KW - aorta AU - Piqueras, Laura AU - Reynolds, Andrew AU - Hodivala-Dilke, Kairbaan AU - Alfranca, Arantzazu AU - Redondo, Juan AU - Hatae, Toshihisa AU - Tanabe, Tadashi AU - Warner, Timothy AU - Bishop-Bailey, David PY - 2007/01/01/ UR - http://dx.doi.org/10.1161/01.ATV.0000250972.83623.61 ER -