ArticleAmerican journal of physiology. Heart and circulatory physiology2014
Mechanisms of vascular dysfunction in mice with endothelium-specific deletion of the PPAR-δ gene.
Article in American journal of physiology. Heart and circulatory physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 22 citations in OpenAlex.
- Expression and function of β-site amyloid precursor protein-cleaving enzyme 2 in vascular endothelium.American journal of physiology. Heart and circulatory physiology · 2025Article
- Inactivation of BACE1 increases expression of endothelial nitric oxide synthase in cerebrovascular endothelium.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Article
- Endothelial PPARδ facilitates the post-ischemic vascular repair through interaction with HIF1α.Theranostics · 2022Article
- An unusual nicotinamide derivative, 4-pyridone-3-carboxamide ribonucleoside (4PYR), is a novel endothelial toxin and oncometabolite.Experimental & molecular medicine · 2021Article
- Article
- Mechanisms of vascular dysfunction in the interleukin-10-deficient murine model of preeclampsia indicate nitric oxide dysregulation.Kidney international · 2021Article
- The mitochondrial thioredoxin reductase system (TrxR2) in vascular endothelium controls peroxynitrite levels and tissue integrity.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Role of PPARs in Progression of Anxiety: Literature Analysis and Signaling Pathways Reconstruction.PPAR research · 2020Review
- Impaired L-arginine metabolism marks endothelial dysfunction in CD73-deficient mice.Molecular and cellular biochemistry · 2019Article
- Endothelium-specific amyloid precursor protein deficiency causes endothelial dysfunction in cerebral arteries.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Article
- The endocannabinoid system in cardiovascular function: novel insights and clinical implications.Clinical autonomic research : official journal of the Clinical Autonomic Research Society · 2018Review
- PPARNuclear receptor research · 2018Article
- Oleanolic acid ameliorates high glucose-induced endothelial dysfunction via PPARδ activation.Scientific reports · 2017Article
- Role of prostacyclin signaling in endothelial production of soluble amyloid precursor protein-α in cerebral microvessels.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Expression and Processing of Amyloid Precursor Protein in Vascular Endothelium.Physiology (Bethesda, Md.) · 2017Review
- Endothelial HO-1 induction by model TG-rich lipoproteins is regulated through a NOX4-Nrf2 pathway.Journal of lipid research · 2016Article
- Myosin light chain kinase inhibitor ML7 improves vascular endothelial dysfunction via tight junction regulation in a rabbit model of atherosclerosis.Molecular medicine reports · 2015Article
- Restoration of Endothelial Function in Pparα (-/-) Mice by Tempol.PPAR research · 2015Article
- Alzheimer's disease: relevant molecular and physiopathological events affecting amyloid-β brain balance and the putative role of PPARs.Frontiers in aging neuroscience · 2014Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Peroxisome proliferator-activated receptor (PPAR)-δ is a nuclear hormone receptor that is mainly involved in lipid metabolism. Recent studies have suggested that PPAR-δ agonists exert vascular protective effects. The present study was designed to characterize vascular function in mice with genetic inactivation of PPAR-δ in the endothelium. Mice with vascular endothelial cell-specific deletion of the PPAR-δ gene (ePPARδ(-/-) mice) were generated using loxP/Cre technology. ePPARδ(-/-) mice were normotensive and did not display any sign of metabolic syndrome. Endothelium-dependent relaxations to ACh and endothelium-independent relaxations to the nitric oxide (NO) donor diethylammonium (Z)-1-(N,N-diethylamino)diazen-1-ium-1,2-diolate were both significantly impaired in the aorta and carotid arteries of ePPARδ(-/-) mice (P < 0.05). In ePPARδ(-/-) mouse aortas, phosphorylation of endothelial NO synthase at Ser(1177) was significantly decreased (P < 0.05). However, basal levels of cGMP were unexpectedly increased (P < 0.05). Enzymatic activity of GTP-cyclohydrolase I and tetrahydrobiopterin levels were also enhanced in ePPARδ(-/-) mice (P < 0.05). Most notably, endothelium-specific deletion of the PPAR-δ gene significantly decreased protein expressions of catalase and glutathione peroxidase 1 and resulted in increased levels of H2O2 in the aorta (P < 0.05). In contrast, superoxide anion production was unaltered. Moreover, treatment with catalase prevented the endothelial dysfunction and elevation of cGMP detected in aortas of ePPARδ(-/-) mice. The findings suggest that increased levels of cGMP caused by H2O2 impair vasodilator reactivity to endogenous and exogenous NO. We speculate that chronic elevation of H2O2 predisposes PPAR-δ-deficient arteries to oxidative stress and vascular dysfunction.
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