ArticleInvestigative ophthalmology & visual science2014
PPARα regulates mobilization and homing of endothelial progenitor cells through the HIF-1α/SDF-1 pathway.
Article in Investigative ophthalmology & visual science, 2014. 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.
- Fenofibrate attenuates doxorubicin-induced cardiotoxicity in patients with breast cancer: a randomized controlled trial.Naunyn-Schmiedeberg's archives of pharmacology · 2025Trial
- Fenofibrate increases circulating haematopoietic stem cells in people with diabetic retinopathy: a randomised, placebo-controlled trial.Diabetologia · 2021Trial
- Peroxisome Proliferator-Activated Receptor α Deficiency Induces Vascular Pathologies through Endothelial Senescence in Diabetic Retinopathy.The American journal of pathology · 2026Article
- Downregulation of microRNA‑221‑3p promotes angiogenesis of lipoprotein(a)‑injured endothelial progenitor cells by targeting silent information regulator 1 to activate the RAF/MEK/ERK signaling pathway.Molecular medicine reports · 2024Article
- Therapeutic roles of PPARα activation in ocular ischemic diseases.Histology and histopathology · 2023Review
- Prognostic Value of Endothelial Progenitor Cells in Acute Myocardial Infarction Patients.Mediators of inflammation · 2023Article
- The PPARα Regulation of the Gut Physiology in Regard to Interaction with Microbiota, Intestinal Immunity, Metabolism, and Permeability.International journal of molecular sciences · 2022Review
- The role of peroxisome proliferator-activated receptors in healthy and diseased eyes.Experimental eye research · 2021Review
- Fenofibrate Protects against Retinal Dysfunction in a Murine Model of Common Carotid Artery Occlusion-Induced Ocular Ischemia.Pharmaceuticals (Basel, Switzerland) · 2021Article
- FGF21 promotes ischaemic angiogenesis and endothelial progenitor cells function under diabetic conditions in an AMPK/NAD+-dependent manner.Journal of cellular and molecular medicine · 2021Article
- Fenofibrate attenuates doxorubicin-induced cardiac dysfunction in mice via activating the eNOS/EPC pathway.Scientific reports · 2021Article
- PPAR-α Agonist Fenofibrate Prevented Diabetic Nephropathy by Inhibiting M1 Macrophages via Improving Endothelial Cell Function in db/db Mice.Frontiers in medicine · 2021Article
- PPARα Agonist Oral Therapy in Diabetic Retinopathy.Biomedicines · 2020Review
- Pemafibrate Prevents Retinal Pathological Neovascularization by Increasing FGF21 Level in a Murine Oxygen-Induced Retinopathy Model.International journal of molecular sciences · 2019Article
- Wnt Signaling in vascular eye diseases.Progress in retinal and eye research · 2019Review
- Article
- Fenofibrate Inhibits Cytochrome P450 Epoxygenase 2C Activity to Suppress Pathological Ocular Angiogenesis.EBioMedicine · 2016Article
- Pharmacologic Activation of Wnt Signaling by Lithium Normalizes Retinal Vasculature in a Murine Model of Familial Exudative Vitreoretinopathy.The American journal of pathology · 2016Article
- Transplantation of EPCs overexpressing PDGFR-β promotes vascular repair in the early phase after vascular injury.BMC cardiovascular disorders · 2016Article
- Deficiency of aldose reductase attenuates inner retinal neuronal changes in a mouse model of retinopathy of prematurity.Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie · 2015Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
Abstract
purposeThe mechanism for the antiangiogenic activity of peroxisome proliferator-activated receptor alpha (PPARα) remains incompletely understood. Endothelial progenitor cells (EPC) are known to participate in neovascularization (NV). The purpose of this study was to investigate whether PPARα regulates EPC during retinal NV.
methodsRetinal NV was induced by oxygen-induced retinopathy (OIR). Mice with OIR were injected intraperitoneally with the PPARα agonist fenofibric acid (FA) or with adenovirus expressing PPARα (Ad-PPARα). Flow cytometry was used to quantify circulating and retinal EPC. Serum stromal cell-derived factor 1 (SDF-1) levels were measured by ELISA. Hypoxia was induced in primary human retinal capillary endothelial cells (HRCEC) and mouse brain endothelial cells (MBEC) by CoCl2. Levels of SDF-1 and hypoxia-inducible factor 1 alpha (HIF-1α) were measured by Western blotting.
resultsFenofibric acid and overexpression of PPARα attenuated the increase of circulating and retinal EPC, correlating with suppressed retinal NV in OIR mice at P17. The PPARα knockout enhanced the OIR-induced increase of circulating and retinal EPC. Fenofibric acid decreased retinal HIF-1α and SDF-1 levels as well as serum SDF-1 levels in the OIR model. In HRCEC, PPARα inhibited HIF-1α nuclear translocation and SDF-1 overexpression induced by hypoxia. Further, MBEC from PPARα(-/-) mice showed more prominent activation of HIF-1α and overexpression of SDF-1 induced by hypoxia, compared with the wild-type (WT) MBEC. PPARα failed to block SDF-1 overexpression induced by a constitutively active mutant of HIF-1α, suggesting that regulation of SDF-1 by PPARα was through blockade of HIF-1α activation.
conclusionsPeroxisome proliferator-activated receptor alpha suppresses ischemia-induced EPC mobilization and homing through inhibition of the HIF-1α/SDF-1 pathway. This represents a novel molecular mechanism for PPARα's antiangiogenic effects.
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