20 results on '"Guimbal S"'
Search Results
2. Desert Hedgehog-related endothelial dysfunction is sufficient to induce diastolic dysfunction
- Author
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Rouault, P., primary, Guimbal, S., additional, Laurianne, C., additional, Mora, P., additional, Chapouly, C., additional, Gadeau, A.P., additional, and Renault, M., additional
- Published
- 2021
- Full Text
- View/download PDF
3. Desert Hedgehog promotes endothelium integrity through ADAM17 degradation
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Rouault, P., primary, Guimbal, S., additional, Cornuault, L., additional, Mora, P., additional, Chapouly, C., additional, Gadeau, A.P., additional, and Renault, M., additional
- Published
- 2021
- Full Text
- View/download PDF
4. Pericyte coverage of cardiac capillaries is decreased in diabetic obese mice
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Cornuault, L., primary, Guimbal, S., additional, Hollier, P.L., additional, Chapouly, C., additional, Gadeau, A.P., additional, Couffinhal, T., additional, and Renault, M.A., additional
- Published
- 2020
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5. A novel murine model for endothelial dysfunction and Heart Failure with Preserved Ejection Fraction
- Author
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Abelanet, A., primary, Guimbal, S., additional, Renault, M.A., additional, Couffinhal, T., additional, and Duplàa, C., additional
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- 2020
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- View/download PDF
6. Endothelial Desert Hedgehog and ectopic Sonic Hedgehog act antagonistically to regulate vessel integrity and angiogenesis
- Author
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Hollier, P.L., primary, Chapouly, C., additional, Guimbal, S., additional, Cornuault, L., additional, Renault, M.A., additional, and Gadeau, A.P., additional
- Published
- 2020
- Full Text
- View/download PDF
7. A novel murine model for endothelial dysfunction and heart failure with preserved ejection fraction
- Author
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Abelanet, A., primary, Guimbal, S., additional, Renault, M.A., additional, Couffinhal, T., additional, and Duplàa, C., additional
- Published
- 2019
- Full Text
- View/download PDF
8. Leptin receptor deficient female mice as a mouse model of heart failure with preserve ejection fraction
- Author
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Guimbal, S., primary, Couffinhal, T., additional, Hollier, P.L., additional, Chapouly, C., additional, Caradu, C., additional, Gadeau, A.P., additional, and Renault, M.A., additional
- Published
- 2019
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9. Endothelial Desert Hedgehog and ectopic Sonic Hedgehog act antagonistically to regulate blood vessel integrity and angiogenesis
- Author
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Hollier, P.L., primary, Chapouly, C., additional, Guimbal, S., additional, Caradu, C., additional, Gadeau, A.P., additional, and Renault, M.A., additional
- Published
- 2019
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10. Alirocumab decreases plasma Lp(a) levels without enhancing Lp(a) liver uptake in vivo
- Author
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Beeske, S., primary, Poirier, B., additional, Villard, E.F., additional, Le Bail, J.C., additional, Dargazanli, G., additional, Tran, T.T.T., additional, Ho-Van Guimbal, S., additional, Bayard, A., additional, Tirode, F., additional, Boulay, D., additional, Bergis, O., additional, Lambert, G., additional, Pruniaux, M.P., additional, Janiak, P., additional, and Guillot, E., additional
- Published
- 2018
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11. Thrombosis in the Coronary Microvasculature Impairs Cardiac Relaxation and Induces Diastolic Dysfunction.
- Author
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Rouault P, Guimbal S, Cornuault L, Bourguignon C, Foussard N, Alzieu P, Choveau F, Benoist D, Chapouly C, Gadeau AP, Couffinhal T, and Renault MA
- Subjects
- Animals, Female, Mice, Ventricular Function, Left, Stroke Volume, Hedgehog Proteins, Microvessels, Aspirin, Diabetes Mellitus, Type 2 complications, Ventricular Dysfunction, Left genetics, Cardiomyopathies, Heart Failure, Thrombosis complications
- Abstract
Background: Heart failure with preserved ejection fraction is proposed to be caused by endothelial dysfunction in cardiac microvessels. Our goal was to identify molecular and cellular mechanisms underlying the development of cardiac microvessel disease and diastolic dysfunction in the setting of type 2 diabetes., Methods: We used Lepr
db/db (leptin receptor-deficient) female mice as a model of type 2 diabetes and heart failure with preserved ejection fraction and identified Hhipl1 (hedgehog interacting protein-like 1), which encodes for a decoy receptor for HH (hedgehog) ligands as a gene upregulated in the cardiac vascular fraction of diseased mice., Results: We then used Dhh (desert HH)-deficient mice to investigate the functional consequences of impaired HH signaling in the adult heart. We found that Dhh -deficient mice displayed increased end-diastolic pressure while left ventricular ejection fraction was comparable to that of control mice. This phenotype was associated with a reduced exercise tolerance in the treadmill test, suggesting that Dhh -deficient mice do present heart failure. At molecular and cellular levels, impaired cardiac relaxation in DhhECKO mice was associated with a significantly decreased PLN (phospholamban) phosphorylation on Thr17 (threonine 17) and an alteration of sarcomeric shortening ex vivo. Besides, as expected, Dhh -deficient mice exhibited phenotypic changes in their cardiac microvessels including a prominent prothrombotic phenotype. Importantly, aspirin therapy prevented the occurrence of both diastolic dysfunction and exercise intolerance in these mice. To confirm the critical role of thrombosis in the pathophysiology of diastolic dysfunction, we verified Leprdb/db also displays increased cardiac microvessel thrombosis. Moreover, consistently, with Dhh -deficient mice, we found that aspirin treatment decreased end-diastolic pressure and improved exercise tolerance in Leprdb/db mice., Conclusions: Altogether, these results demonstrate that microvessel thrombosis may participate in the pathophysiology of heart failure with preserved ejection fraction., Competing Interests: Disclosures None.- Published
- 2024
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12. Intrinsic blood-brain barrier dysfunction contributes to multiple sclerosis pathogenesis.
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Nishihara H, Perriot S, Gastfriend BD, Steinfort M, Cibien C, Soldati S, Matsuo K, Guimbal S, Mathias A, Palecek SP, Shusta EV, Pasquier RD, and Engelhardt B
- Subjects
- Humans, Blood-Brain Barrier pathology, Cells, Cultured, Brain physiology, Multiple Sclerosis pathology, Induced Pluripotent Stem Cells metabolism
- Abstract
Blood-brain barrier (BBB) breakdown and immune cell infiltration into the CNS are early hallmarks of multiple sclerosis (MS). The mechanisms leading to BBB dysfunction are incompletely understood and generally thought to be a consequence of neuroinflammation. Here, we have challenged this view and asked if intrinsic alterations in the BBB of MS patients contribute to MS pathogenesis. To this end, we made use of human induced pluripotent stem cells derived from healthy controls and MS patients and differentiated them into brain microvascular endothelial cell (BMEC)-like cells as in vitro model of the BBB. MS-derived BMEC-like cells showed impaired junctional integrity, barrier properties and efflux pump activity when compared to healthy controls. Also, MS-derived BMEC-like cells displayed an inflammatory phenotype with increased adhesion molecule expression and immune cell interactions. Activation of Wnt/β-catenin signalling in MS-derived endothelial progenitor cells enhanced barrier characteristics and reduced the inflammatory phenotype. Our study provides evidence for an intrinsic impairment of BBB function in MS patients that can be modelled in vitro. Human iPSC-derived BMEC-like cells are thus suitable to explore the molecular underpinnings of BBB dysfunction in MS and will assist in the identification of potential novel therapeutic targets for BBB stabilization., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2022
- Full Text
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13. Full-length Dhh and N-terminal Shh act as competitive antagonists to regulate angiogenesis and vascular permeability.
- Author
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Hollier PL, Chapouly C, Diop A, Guimbal S, Cornuault L, Gadeau AP, and Renault MA
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- Animals, Astrocytes drug effects, Astrocytes pathology, Cells, Cultured, Corneal Neovascularization genetics, Corneal Neovascularization pathology, Encephalomyelitis, Autoimmune, Experimental genetics, Encephalomyelitis, Autoimmune, Experimental pathology, Endothelial Cells drug effects, Endothelial Cells pathology, Female, Hedgehog Proteins administration & dosage, Hedgehog Proteins genetics, Ligands, Male, Mice, Knockout, Patched-1 Receptor metabolism, Protein Binding, Signal Transduction, Smoothened Receptor genetics, Smoothened Receptor metabolism, Mice, Astrocytes metabolism, Capillary Permeability drug effects, Cerebral Cortex blood supply, Corneal Neovascularization metabolism, Encephalomyelitis, Autoimmune, Experimental metabolism, Endothelial Cells metabolism, Hedgehog Proteins metabolism, Neovascularization, Pathologic
- Abstract
Aims: The therapeutic potential of Hedgehog (Hh) signalling agonists for vascular diseases is of growing interest. However, molecular and cellular mechanisms underlying the role of the Hh signalling in vascular biology remain poorly understood. The purpose of the present article is to clarify some conflicting literature data., Methods and Results: With this goal, we have demonstrated that, unexpectedly, ectopically administered N-terminal Sonic Hh (N-Shh) and endogenous endothelial-derived Desert Hh (Dhh) induce opposite effects in endothelial cells (ECs). Notably, endothelial Dhh acts under its full-length soluble form (FL-Dhh) and activates Smoothened in ECs, while N-Shh inhibits it. At molecular level, N-Shh prevents FL-Dhh binding to Patched-1 (Ptch1) demonstrating that N-Shh acts as competitive antagonist to FL-Dhh. Besides, we found that even though FL-Hh ligands and N-Hh ligands all bind Ptch1, they induce distinct Ptch1 localization. Finally, we confirmed that in a pathophysiological setting, i.e. brain inflammation, astrocyte-derived N-Shh acts as a FL-Dhh antagonist., Conclusion: The present study highlights for the first time that FL-Dhh and N-Hh ligands have antagonistic properties especially in ECs., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2020. For permissions, please email: journals.permissions@oup.com.)
- Published
- 2021
- Full Text
- View/download PDF
14. Mast Cells Are the Trigger of Small Vessel Disease and Diastolic Dysfunction in Diabetic Obese Mice.
- Author
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Guimbal S, Cornuault L, Rouault P, Hollier PL, Chapouly C, Bats ML, Imbault J, Gadeau AP, Couffinhal T, and Renault MA
- Subjects
- Animals, Cells, Cultured, Coronary Vessels immunology, Coronary Vessels pathology, Diastole, Disease Models, Animal, Female, Heart Failure immunology, Heart Failure metabolism, Heart Failure physiopathology, Histamine Release, Humans, Mast Cells immunology, Mast Cells pathology, Mice, Knockout, Myocardium immunology, Myocardium metabolism, Myocardium pathology, Obesity immunology, Obesity metabolism, Receptors, Leptin deficiency, Receptors, Leptin genetics, Ventricular Dysfunction, Left immunology, Ventricular Dysfunction, Left metabolism, Ventricular Dysfunction, Left physiopathology, Mice, Cell Degranulation, Coronary Vessels metabolism, Diabetes Mellitus genetics, Diabetes Mellitus immunology, Diabetes Mellitus metabolism, Heart Failure etiology, Mast Cells metabolism, Obesity complications, Ventricular Dysfunction, Left etiology, Ventricular Function, Left
- Abstract
[Figure: see text].
- Published
- 2021
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15. Desert Hedgehog-Driven Endothelium Integrity Is Enhanced by Gas1 (Growth Arrest-Specific 1) but Negatively Regulated by Cdon (Cell Adhesion Molecule-Related/Downregulated by Oncogenes).
- Author
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Chapouly C, Hollier PL, Guimbal S, Cornuault L, Gadeau AP, and Renault MA
- Subjects
- Animals, Antigens, CD genetics, Antigens, CD metabolism, Blood-Brain Barrier pathology, Cadherins genetics, Cadherins metabolism, Cell Adhesion Molecules deficiency, Cell Adhesion Molecules genetics, Cell Cycle Proteins deficiency, Cell Cycle Proteins genetics, Cells, Cultured, Corneal Neovascularization genetics, Corneal Neovascularization pathology, Disease Models, Animal, Endothelial Cells pathology, Endothelium, Corneal pathology, Female, GPI-Linked Proteins deficiency, GPI-Linked Proteins genetics, GPI-Linked Proteins metabolism, Hedgehog Proteins genetics, Humans, Inflammation genetics, Inflammation pathology, Male, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Patched-1 Receptor metabolism, Signal Transduction, Smoothened Receptor metabolism, Blood-Brain Barrier metabolism, Cell Adhesion Molecules metabolism, Cell Cycle Proteins metabolism, Corneal Neovascularization metabolism, Endothelial Cells metabolism, Endothelium, Corneal metabolism, Hedgehog Proteins metabolism, Inflammation metabolism
- Abstract
Objective: Evidences accumulated within the past decades identified hedgehog signaling as a new regulator of endothelium integrity. More specifically, we recently identified Dhh (desert hedgehog) as a downstream effector of Klf2 (Kruppel-like factor 2) in endothelial cells (ECs). The purpose of this study is to investigate whether hedgehog coreceptors Gas1 (growth arrest-specific 1) and Cdon (cell adhesion molecule-related/downregulated by oncogenes) may be used as therapeutic targets to modulate Dhh signaling in ECs. Approach and Results: We demonstrated that both Gas1 and Cdon are expressed in adult ECs and relied on either siRNAs- or EC-specific conditional knockout mice to investigate their role. We found that Gas1 deficiency mainly phenocopies Dhh deficiency especially by inducing VCAM-1 (vascular cell adhesion molecule 1) and ICAM-1 (intercellular adhesion molecule 1) overexpression while Cdon deficiency has opposite effects by promoting endothelial junction integrity. At a molecular level, Cdon prevents Dhh binding to Ptch1 (patched-1) and thus acts as a decoy receptor for Dhh, while Gas1 promotes Dhh binding to Smo (smoothened) and as a result potentiates Dhh effects. Since Cdon is upregulated in ECs treated by inflammatory cytokines, including TNF (tumor necrosis factor)-α and Il (interleukin)-1β, we then tested whether Cdon inhibition would promote endothelium integrity in acute inflammatory conditions and found that both fibrinogen and IgG extravasation were decreased in association with an increased Cdh5 (cadherin-5) expression in the brain cortex of EC-specific Cdon knockout mice administered locally with Il-1β., Conclusions: Altogether, these results demonstrate that Gas1 is a positive regulator of Dhh in ECs while Cdon is a negative regulator. Interestingly, Cdon blocking molecules may then be used to promote endothelium integrity, at least in inflammatory conditions.
- Published
- 2020
- Full Text
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16. Blood-brain barrier genetic disruption leads to protective barrier formation at the Glia Limitans.
- Author
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Mora P, Hollier PL, Guimbal S, Abelanet A, Diop A, Cornuault L, Couffinhal T, Horng S, Gadeau AP, Renault MA, and Chapouly C
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- Adherens Junctions pathology, Adherens Junctions physiology, Animals, Antigens, CD genetics, Antigens, CD physiology, Astrocytes pathology, Astrocytes physiology, Cadherins genetics, Cadherins physiology, Capillary Permeability genetics, Capillary Permeability physiology, Claudin-5 genetics, Claudin-5 physiology, Down-Regulation, Encephalomyelitis, Autoimmune, Experimental genetics, Encephalomyelitis, Autoimmune, Experimental pathology, Encephalomyelitis, Autoimmune, Experimental physiopathology, Endothelial Cells pathology, Endothelial Cells physiology, Female, Hedgehog Proteins deficiency, Hedgehog Proteins genetics, Hedgehog Proteins physiology, Humans, Mice, Mice, Inbred C57BL, Mice, Knockout, Multiple Sclerosis pathology, Multiple Sclerosis physiopathology, Neuroglia pathology, Neuroglia physiology, Tight Junctions pathology, Tight Junctions physiology, Blood-Brain Barrier physiology, Blood-Brain Barrier physiopathology
- Abstract
Inflammation of the central nervous system (CNS) induces endothelial blood-brain barrier (BBB) opening as well as the formation of a tight junction barrier between reactive astrocytes at the Glia Limitans. We hypothesized that the CNS parenchyma may acquire protection from the reactive astrocytic Glia Limitans not only during neuroinflammation but also when BBB integrity is compromised in the resting state. Previous studies found that astrocyte-derived Sonic hedgehog (SHH) stabilizes the BBB during CNS inflammatory disease, while endothelial-derived desert hedgehog (DHH) is expressed at the BBB under resting conditions. Here, we investigated the effects of endothelial Dhh on the integrity of the BBB and Glia Limitans. We first characterized DHH expression within endothelial cells at the BBB, then demonstrated that DHH is down-regulated during experimental autoimmune encephalomyelitis (EAE). Using a mouse model in which endothelial Dhh is inducibly deleted, we found that endothelial Dhh both opens the BBB via the modulation of forkhead box O1 (FoxO1) transcriptional activity and induces a tight junctional barrier at the Glia Limitans. We confirmed the relevance of this glial barrier system in human multiple sclerosis active lesions. These results provide evidence for the novel concept of "chronic neuroinflammatory tolerance" in which BBB opening in the resting state is sufficient to stimulate a protective barrier at the Glia Limitans that limits the severity of subsequent neuroinflammatory disease. In summary, genetic disruption of the BBB generates endothelial signals that drive the formation under resting conditions of a secondary barrier at the Glia Limitans with protective effects against subsequent CNS inflammation. The concept of a reciprocally regulated CNS double barrier system has implications for treatment strategies in both the acute and chronic phases of multiple sclerosis pathophysiology., Competing Interests: The authors have declared that no competing interests exist.
- Published
- 2020
- Full Text
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17. Lipoprotein(a) Cellular Uptake Ex Vivo and Hepatic Capture In Vivo Is Insensitive to PCSK9 Inhibition With Alirocumab.
- Author
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Chemello K, Beeské S, Trang Tran TT, Blanchard V, Villard EF, Poirier B, Le Bail JC, Dargazanli G, Ho-Van-Guimbal S, Boulay D, Bergis O, Pruniaux MP, Croyal M, Janiak P, Guillot E, and Lambert G
- Abstract
Lipoprotein(a) (Lp[a]) is the most common genetically inherited risk factor for cardiovascular disease. Many aspects of Lp(a) metabolism remain unknown. We assessed the uptake of fluorescent Lp(a) in primary human lymphocytes as well as Lp(a) hepatic capture in a mouse model in which endogenous hepatocytes have been ablated and replaced with human ones. Modulation of LDLR expression with the PCSK9 inhibitor alirocumab did not alter the cellular or the hepatic uptake of Lp(a), demonstrating that the LDL receptor is not a major route for Lp(a) plasma clearance. These results have clinical implications because they underpin why statins are not efficient at reducing Lp(a)., (© 2020 The Authors.)
- Published
- 2020
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18. Dock5 is a new regulator of microtubule dynamic instability in osteoclasts.
- Author
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Guimbal S, Morel A, Guérit D, Chardon M, Blangy A, and Vives V
- Subjects
- Animals, Cells, Cultured, Mice, Mice, Inbred C57BL, Neuropeptides antagonists & inhibitors, Osteoclasts cytology, rac1 GTP-Binding Protein antagonists & inhibitors, Bone Resorption metabolism, Guanine Nucleotide Exchange Factors physiology, Microtubules metabolism, Osteoclasts metabolism, Tubulin metabolism
- Abstract
Background Information: Osteoclast resorption is dependent on a podosome-rich structure called sealing zone. It tightly attaches the osteoclast to the bone creating a favourable acidic microenvironment for bone degradation. This adhesion structure needs to be stabilised by microtubules whose acetylation is maintained by down-regulation of deacetylase HDAC6 and/or of microtubule destabilising kinase GSK3β activities. We already established that Dock5 is a guanine nucleotide exchange factor for Rac1. As a consequence, Dock5 inhibition results in a decrease of the GTPase activity associated with impaired podosome assembly into sealing zones and resorbing activity in osteoclasts. More, administration of C21, a chemical compound that directly inhibits the exchange activity of Dock5, disrupts osteoclast podosome organisation and protects mice against bone degradation in models recapitulating major osteolytic diseases., Results: In this report, we show that Dock5 knockout osteoclasts also present a reduced acetylated tubulin level leading to a decreased length and duration of microtubule growth phases, whereas their growth speed remains unaffected. Dock5 does not act by direct interaction with the polymerised tubulin. Using specific Rac inhibitors, we showed that Dock5 regulates microtubule dynamic instability through Rac-dependent and -independent pathways. The latter involves GSK3β inhibitory serine 9 phosphorylation downstream of Akt activation but not HDAC6 activity., Conclusion: We showed that Dock5 is a new regulator of microtubule dynamic instability in osteoclast., Significance: Dock5 dual role in the regulation of the actin cytoskeleton and microtubule, which both need to be intact for bone resorption, reinforces the fact that it is an interesting therapeutic target for osteolytic pathologies., (© 2019 Société Française des Microscopies and Société de Biologie Cellulaire de France. Published by John Wiley & Sons Ltd.)
- Published
- 2019
- Full Text
- View/download PDF
19. Role of Hedgehog Signaling in Vasculature Development, Differentiation, and Maintenance.
- Author
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Chapouly C, Guimbal S, Hollier PL, and Renault MA
- Subjects
- Animals, Blood-Brain Barrier metabolism, Cell Differentiation, Humans, Ligands, Neovascularization, Physiologic, Blood Vessels embryology, Blood Vessels metabolism, Hedgehog Proteins metabolism, Organogenesis, Signal Transduction
- Abstract
The role of Hedgehog (Hh) signaling in vascular biology has first been highlighted in embryos by Pepicelli et al. in 1998 and Rowitch et al. in 1999. Since then, the proangiogenic role of the Hh ligands has been confirmed in adults, especially under pathologic conditions. More recently, the Hh signaling has been proposed to improve vascular integrity especially at the blood-brain barrier (BBB). However, molecular and cellular mechanisms underlying the role of the Hh signaling in vascular biology remain poorly understood and conflicting results have been reported. As a matter of fact, in several settings, it is currently not clear whether Hh ligands promote vessel integrity and quiescence or destabilize vessels to promote angiogenesis. The present review relates the current knowledge regarding the role of the Hh signaling in vasculature development, maturation and maintenance, discusses the underlying proposed mechanisms and highlights controversial data which may serve as a guideline for future research. Most importantly, fully understanding such mechanisms is critical for the development of safe and efficient therapies to target the Hh signaling in both cancer and cardiovascular/cerebrovascular diseases.
- Published
- 2019
- Full Text
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20. Restoring Endothelial Function by Targeting Desert Hedgehog Downstream of Klf2 Improves Critical Limb Ischemia in Adults.
- Author
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Caradu C, Couffinhal T, Chapouly C, Guimbal S, Hollier PL, Ducasse E, Bura-Rivière A, Dubois M, Gadeau AP, and Renault MA
- Subjects
- Animals, Autocrine Communication, Capillary Permeability, Cells, Cultured, Critical Illness, Cyclohexylamines pharmacology, Cytokines metabolism, Disease Models, Animal, Endothelial Cells drug effects, Gene Expression Regulation, Hedgehog Proteins deficiency, Hedgehog Proteins genetics, Hindlimb, Human Umbilical Vein Endothelial Cells metabolism, Humans, Inflammation Mediators metabolism, Ischemia drug therapy, Ischemia genetics, Ischemia physiopathology, Kruppel-Like Transcription Factors genetics, Male, Mice, Inbred C57BL, Mice, Knockout, Regional Blood Flow, Signal Transduction, Stress, Mechanical, Thiophenes pharmacology, Endothelial Cells metabolism, Hedgehog Proteins metabolism, Ischemia metabolism, Kruppel-Like Transcription Factors metabolism, Muscle, Skeletal blood supply, Neovascularization, Physiologic drug effects
- Abstract
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.
- Published
- 2018
- Full Text
- View/download PDF
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