ArticleHypertension (Dallas, Tex. : 1979)2011
Activation of peroxisome proliferator-activated receptor-{delta} enhances regenerative capacity of human endothelial progenitor cells by stimulating biosynthesis of tetrahydrobiopterin.
Article in Hypertension (Dallas, Tex. : 1979), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 36 citations in OpenAlex.
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- Shear Stress Triggers Angiogenesis of Late Endothelial Progenitor Cells via the PTEN/Akt/GTPCH/BH4 Pathway.Stem cells international · 2020Article
- PPARδ agonist prevents endothelial dysfunction via induction of dihydrofolate reductase gene and activation of tetrahydrobiopterin salvage pathway.British journal of pharmacology · 2019Article
- PPARβ/δ: Linking Metabolism to Regeneration.International journal of molecular sciences · 2018Review
- 6-Gingerol Normalizes the Expression of Biomarkers Related to Hypertension via PPARPPAR research · 2018Article
- Live cell screening platform identifies PPARδ as a regulator of cardiomyocyte proliferation and cardiac repair.Cell research · 2017Article
- Oleanolic acid ameliorates high glucose-induced endothelial dysfunction via PPARδ activation.Scientific reports · 2017Article
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- Uncoupling of endothelial nitric oxide synthase in cerebral vasculature of Tg2576 mice.Journal of neurochemistry · 2015Article
- Parkinson's disease in GTP cyclohydrolase 1 mutation carriers.Brain : a journal of neurology · 2015Article
- Regulating PPARδ signaling as a potential therapeutic strategy for skeletal muscle disorders in heart failure.American journal of physiology. Heart and circulatory physiology · 2015Article
- Activation of PPARδ prevents endothelial dysfunction induced by overexpression of amyloid-β precursor protein.Cardiovascular research · 2012Article
- Article
- PPARδ agonist GW501516 prevents uncoupling of endothelial nitric oxide synthase in cerebral microvessels of hph-1 mice.Brain research · 2012Article
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5 authors at 1 institution in 1 country.
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Abstract
The mechanisms underlying the regenerative capacity of endothelial progenitor cells (EPCs) are not fully understood. We hypothesized that biosynthesis of tetrahydrobiopterin is an important mechanism responsible for the stimulatory effects of peroxisome proliferator-activated receptor-δ (PPARδ) activation on regenerative function of human EPCs. Treatment of human EPCs with a selective PPARδ agonist GW501516 for 24 hours increased the levels of mRNA, protein, and enzymatic activity of GTP cyclohydrolase I (GTPCH I), as well as the production of tetrahydrobiopterin. The effects of GW501516 were mediated by suppression of PTEN expression, thereby increasing phosphorylation of AKT. The AKT signaling also mediated GW501516-induced phosphorylation of endothelial NO synthase. In addition, activation of PPARδ significantly enhanced proliferation of EPCs. This effect was abolished by the GTPCH I inhibitor, 2,4-diamino-6-hydroxypyrimidine, or genetic inactivation of GTPCH I with small interfering RNA but not by inhibition of endothelial NO synthase with N(G)-nitro-l-arginine methyl ester. Supplementation of NO did not reverse 2,4-diamino-6-hydroxypyrimidine-inhibited 5-bromodeoxyuridine incorporation. Furthermore, transplantation of human EPCs stimulated re-endothelialization in a mouse model of carotid artery injury. Pretreatment of EPCs with GW501516 significantly enhanced the ability of transplanted EPCs to repair denuded endothelium. GTPCH I-small interfering RNA transfection significantly inhibited in vivo regenerative capacity of EPCs stimulated with GW501516. Thus, in human EPCs, activation of PPARδ stimulates expression and activity of GTPCH I and biosynthesis of tetrahydrobiopterin via PTEN-AKT signaling pathway. This effect enhances the regenerative function of EPCs.
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