Restoring Endothelial Function by Targeting Desert Hedgehog Downstream of Klf2 Improves Critical Limb Ischemia in Adults
| dc.rights.license | open | en_US |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | CARADU, Caroline | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | COUFFINHAL, Thierry | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | CHAPOULY, Candice | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | GUIMBAL, Sarah | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | HOLLIER, Pierre-Louis | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | DUCASSE, Eric | |
| dc.contributor.author | BURA-RIVIÈRE, Alessandra | |
| dc.contributor.author | DUBOIS, Mathilde | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | GADEAU, Alain-Pierre | |
| hal.structure.identifier | Biologie des maladies cardiovasculaires = Biology of Cardiovascular Diseases | |
| dc.contributor.author | RENAULT, Marie-Ange | |
| dc.date.accessioned | 2020 | |
| dc.date.available | 2020 | |
| dc.date.issued | 2018 | |
| dc.identifier.issn | 1524-4571 | en_US |
| dc.identifier.uri | https://oskar-bordeaux.fr/handle/20.500.12278/20882 | |
| dc.description.abstractEn | RATIONALE: Klf (kruppel-like factor) 2 is critical to establish and maintain endothelial integrity. OBJECTIVE: Therefore, determining upstream and downstream mediators of Klf2 would lead to alternative therapeutic targets in cardiovascular disease management. METHODS AND RESULTS: Here we identify Dhh (desert hedgehog) as a downstream effector of Klf2, whose expression in endothelial cells (ECs) is upregulated by shear stress and decreased by inflammatory cytokines. Consequently, we show that Dhh knockdown in ECs promotes endothelial permeability and EC activation and that Dhh agonist prevents TNF-α (tumor necrosis factor alpha) or glucose-induced EC dysfunction. Moreover, we demonstrate that human critical limb ischemia, a pathological condition linked to diabetes mellitus and inflammation, is associated to major EC dysfunction. By recreating a complex model of critical limb ischemia in diabetic mice, we found that Dhh-signaling agonist significantly improved EC function without promoting angiogenesis, which subsequently improved muscle perfusion. CONCLUSION: Restoring EC function leads to significant critical limb ischemia recovery. Dhh appears to be a promising target, downstream of Klf2, to prevent the endothelial dysfunction involved in ischemic vascular diseases. | |
| dc.language.iso | EN | en_US |
| dc.subject | Article RECHERCHE | |
| dc.subject.en | Animal | |
| dc.subject.en | Animals | |
| dc.subject.en | Autocrine Communication | |
| dc.subject.en | Capillary Permeability | |
| dc.subject.en | Cells | |
| dc.subject.en | Critical Illness | |
| dc.subject.en | Cultured | |
| dc.subject.en | Cyclohexylamines | |
| dc.subject.en | Cytokines | |
| dc.subject.en | Disease Models | |
| dc.subject.en | Endothelial cells | |
| dc.subject.en | Endothelial Cells | |
| dc.subject.en | Gene Expression Regulation | |
| dc.subject.en | Hedgehog Proteins | |
| dc.subject.en | hedgehogs | |
| dc.subject.en | Hindlimb | |
| dc.subject.en | Human Umbilical Vein Endothelial Cells | |
| dc.subject.en | Humans | |
| dc.subject.en | Inbred C57BL | |
| dc.subject.en | inflammation | |
| dc.subject.en | Inflammation Mediators | |
| dc.subject.en | Ischemia | |
| dc.subject.en | Knockout | |
| dc.subject.en | Kruppel-Like Transcription Factors | |
| dc.subject.en | Male | |
| dc.subject.en | Mechanical | |
| dc.subject.en | Mice | |
| dc.subject.en | Muscle | |
| dc.subject.en | Neovascularization | |
| dc.subject.en | peripheral arterial disease | |
| dc.subject.en | Physiologic | |
| dc.subject.en | Regional Blood Flow | |
| dc.subject.en | Signal Transduction | |
| dc.subject.en | Skeletal | |
| dc.subject.en | Stress | |
| dc.subject.en | therapeutics | |
| dc.subject.en | Thiophenes | |
| dc.title.en | Restoring Endothelial Function by Targeting Desert Hedgehog Downstream of Klf2 Improves Critical Limb Ischemia in Adults | |
| dc.type | Article de revue | en_US |
| dc.identifier.doi | 10.1161/CIRCRESAHA.118.313177 | en_US |
| dc.subject.hal | Sciences du Vivant [q-bio]/Médecine humaine et pathologie | en_US |
| dc.identifier.pubmed | 30355159 | en_US |
| bordeaux.journal | Circulation Research | en_US |
| bordeaux.page | 1053–1065 | en_US |
| bordeaux.volume | 123 | en_US |
| bordeaux.hal.laboratories | Biologie des maladies cardiovasculaires - U1034 | en_US |
| bordeaux.issue | 9 | en_US |
| bordeaux.institution | Université de Bordeaux | en_US |
| bordeaux.peerReviewed | oui | en_US |
| bordeaux.inpress | non | en_US |
| hal.export | false | |
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