Full-length dhh and N-terminal shh act as competitive antagonists to regulate angiogenesis and vascular permeability.

Abstract:

: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. AIMS:The purpose of the present paper is to clarify some conflicting literature data. METHODS AND RESULTS:: With this goal we have demonstrated that, unexpectedly, ectopically administered N-terminal Sonic Hedgehog (N-Shh) and endogenous endothelial-derived Desert Hedgehog (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 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 Patched-1, they induce distinct Patched-1 localization. Finally, we confirmed that in a pathophysiological setting i.e. brain inflammation, astrocyte-derived N-Shh act 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. TRANSLATIONAL PERSPECTIVE:As a consequence, Hh ligands or forms of Hh ligands cannot be used instead of another for therapeutic purposes.

journal_name

Cardiovasc Res

journal_title

Cardiovascular research

authors

Hollier PL,Chapouly C,Diop A,Guimbal S,Cornuault L,Gadeau AP,Renault MA

doi

10.1093/cvr/cvaa285

subject

Has Abstract

pub_date

2020-10-16 00:00:00

eissn

0008-6363

issn

1755-3245

pii

5924557

pub_type

杂志文章
  • Left atrial pacing induces memory and is associated with atrial tachyarrhythmias.

    abstract:OBJECTIVE:Transiently altering the atrial activation sequence induces atrial memory, manifested as an altered atrial gradient as measured in electrocardiographic XYZ leads. We hypothesized that protracted periods of left atrial impulse initiation alter the atrial gradient in a manner predictive of arrhythmias. METHODS...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(03)00536-4

    authors: Chandra P,Rosen TS,Herweg B,Danilo P Jr,Rosen MR

    更新日期:2003-11-01 00:00:00

  • Influence of ivabradine on reverse remodelling during mechanical unloading.

    abstract:AIMS:Ivabradine (Iva) has shown beneficial structural and functional effects in clinical and experimental heart failure (HF), but its action in combination with mechanical unloading (MU), such as during treatment with left ventricular assist devices (LVAD), is unknown. The aim of this study was to investigate the effec...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvs318

    authors: Navaratnarajah M,Ibrahim M,Siedlecka U,van Doorn C,Shah A,Gandhi A,Dias P,Sarathchandra P,Yacoub MH,Terracciano CM

    更新日期:2013-02-01 00:00:00

  • From genetics to response to injury: vascular smooth muscle cells in aneurysms and dissections of the ascending aorta.

    abstract::Vascular smooth muscle cells (vSMCs) play a crucial role in both the pathogenesis of Aneurysms and Dissections of the ascending thoracic aorta (TAAD) in humans and in the associated adaptive compensatory responses, since thrombosis and inflammatory processes are absent in the majority of cases. Aneurysms and dissectio...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvy006

    authors: Michel JB,Jondeau G,Milewicz DM

    更新日期:2018-03-15 00:00:00

  • Chlamydia pneumoniae infections in mouse models: relevance for atherosclerosis research.

    abstract::Mouse models have been frequently used in the study of Chlamydia pneumoniae (also known as Chlamydophila pneumoniae) infections. This gram-negative obligate intracellular bacterium causes respiratory infections, followed by dissemination of the bacterium to various organs throughout the body, including cardiovascular ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/j.cardiores.2004.09.031

    authors: de Kruif MD,van Gorp EC,Keller TT,Ossewaarde JM,ten Cate H

    更新日期:2005-02-01 00:00:00

  • Repolarization abnormalities and their arrhythmogenic consequences in porcine tachycardia-induced cardiomyopathy.

    abstract:OBJECTIVES:Action potential prolongation related to the alteration of several membrane currents is constantly reported in heart failure (HF) but reports about its role in arrhythmogenesis are sparse. Our aim was to determine, by analogy with long QT syndromes, whether prolonged repolarization is associated with increas...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00236-5

    authors: Lacroix D,Gluais P,Marquié C,D'Hoinne C,Adamantidis M,Bastide M

    更新日期:2002-04-01 00:00:00

  • The ACE2 expression in human heart indicates new potential mechanism of heart injury among patients infected with SARS-CoV-2.

    abstract::A new type of pneumonia caused by a novel coronavirus SARS-CoV-2 outbreaks recently in China and spreads into many other countries. This disease, named as COVID-19, is similar to patients infected by SARS-CoV and MERS-CoV, and nearly 20% of patients developed severe condition. Cardiac injury is a prevalent complicatio...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvaa078

    authors: Chen L,Li X,Chen M,Feng Y,Xiong C

    更新日期:2020-05-01 00:00:00

  • Pharmacological postconditioning effect of muramyl dipeptide is mediated through RIP2 and TAK1.

    abstract:AIMS:Despite their ability to cause septic shock and myocardial dysfunction, components of Gram-negative bacterial cell walls, like lipopolysaccharide, have been shown in numerous studies to induce myocardial protection during ischaemia-reperfusion injury. Muramyl dipeptide (MDP) is another such component recognized by...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvp055

    authors: Sicard P,Jacquet S,Kobayashi KS,Flavell RA,Marber MS

    更新日期:2009-07-15 00:00:00

  • Preventing treatment failures in coronary artery disease: what can we learn from the biology of in-stent restenosis, vein graft failure, and internal thoracic arteries?

    abstract::Coronary artery disease (CAD) remains one of the most important causes of morbidity and mortality worldwide, and the availability of percutaneous or surgical revascularization procedures significantly improves survival. However, both strategies are daunted by complications which limit long-term effectiveness. In-stent...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvz214

    authors: Spadaccio C,Antoniades C,Nenna A,Chung C,Will R,Chello M,Gaudino MFL

    更新日期:2020-03-01 00:00:00

  • Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning?

    abstract:OBJECTIVE:We propose that ischemic preconditioning (IPC) and mitochondrial K(ATP) channel activation protect the myocardium by inhibiting mitochondrial permeability transition pore (MPTP) opening at reperfusion. METHODS:Isolated rat hearts were subjected to 35 min ischemia/120 min reperfusion and assigned to the follo...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00455-8

    authors: Hausenloy DJ,Maddock HL,Baxter GF,Yellon DM

    更新日期:2002-08-15 00:00:00

  • Delayed preconditioning of the human myocardium: signal transduction and clinical implications.

    abstract:OBJECTIVE:Ischemic preconditioning confers cardioprotection in early and delayed phases. We investigated the delayed window of pharmacological and ischemic preconditioning in human myocardium, and the involvement of mitoKATP, PKC and p38MAPK. METHODS:These studies were carried out using human right atrial tissue in a ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2003.10.013

    authors: Loubani M,Hassouna A,Galiñanes M

    更新日期:2004-02-15 00:00:00

  • Indomethacin suppresses the coronary flow response to hypoxia in exercise trained and sedentary rats.

    abstract:STUDY OBJECTIVE:The aim was to determine if prostaglandin like activity might be involved in changes due to exercise training in the coronary flow responses to hypoxia. DESIGN:The coronary flow response to hypoxia was measured under constant perfusion pressure in isolated perfused hearts from 12 endurance exercise tra...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/24.9.733

    authors: Baur TS,Brodowicz GR,Lamb DR

    更新日期:1990-09-01 00:00:00

  • Altered response to ibutilide in a heart failure model.

    abstract:OBJECTIVE:Despite the frequent use of anti-arrhythmic drugs in the general population, the electrophysiologic effects of these agents have not been elucidated in congestive heart failure (CHF). METHODS:To examine the impact of left ventricular dysfunction on actions of type III anti-arrhythmic drugs, we evaluated the ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(00)00235-2

    authors: Chugh SS,Johnson SB,Packer DL

    更新日期:2001-01-01 00:00:00

  • Cardiac transplantation affects ventricular expression of brain natriuretic peptide.

    abstract:OBJECTIVE:The aim was to examine the ventricular expression of brain natriuretic peptide (BNP) in the transplanted human heart. METHODS:Serial right ventricular biopsies (n = 68) and plasma samples (n = 68) were obtained for measurement of BNP and atrial natriuretic peptide (ANP) from 14 orthotopic cardiac transplant ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/27.2.188

    authors: Ationu A,Burch M,Singer D,Littleton P,Carter N

    更新日期:1993-02-01 00:00:00

  • Cardiomegaly and haemodynamics in rats with a transplantable growth hormone-secreting tumour.

    abstract::To investigate cardiovascular changes in experimental acromegaly, a growth hormone-secreting tumour (MtT-W-15) was implanted in adult female rats. Somatic and tumour growth occurred steadily during the 8 week study period, as did an increase in serum growth hormone titre. Weight of left ventricle and right ventricle i...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/19.5.270

    authors: Penney DG,Dunbar JC Jr,Baylerian MS

    更新日期:1985-05-01 00:00:00

  • Effects of nitroglycerin and dipyridamole on acute myocardial infarction: a thermographic study in the dog.

    abstract::The effects on an acute myocardial infarction of equipotent hypotensive doses of nitroglycerin and dipyridamole were studied using the thermographic technique in open-chest dogs. Nitroglycerin did not reduce the cool ischaemic area in any of the nine dogs studied. In six of the dogs, in which the ischaemic region coul...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/13.5.281

    authors: Malm A,Arborelius M Jr,Lilja B,Gil RL,Bornmyr S

    更新日期:1979-05-01 00:00:00

  • Impaired flow-mediated vasodilation of the brachial artery in patients with primary hyperparathyroidism improves after parathyroidectomy.

    abstract:OBJECTIVE:The endothelium is a newly recognised target tissue of parathyroid hormone (PTH). It is not clear whether hyperparathyroidism affects endothelial function and whether parathyroidectomy (Ptx) has an influence on arterial vessel wall properties. We studied brachial flow-mediated vasodilation (FMD) and brachial ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(00)00130-9

    authors: Kosch M,Hausberg M,Vormbrock K,Kisters K,Gabriels G,Rahn KH,Barenbrock M

    更新日期:2000-09-01 00:00:00

  • Pathophysiological significance of coronary collaterals for preservation of the myocardium during coronary occlusion and reperfusion in anaesthetised dogs.

    abstract::The significance of pre-existing coronary collaterals for preservation of the myocardium during coronary occlusion and reperfusion was studied in anaesthetised open-chest dogs. The extent of myocardial ischaemic damage was assessed by the accumulation of calcium in the central zone of the ischaemic area and the size o...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/14.5.288

    authors: Tanabe M,Fujiwara S,Ohta N,Shimamoto N,Hirata M

    更新日期:1980-05-01 00:00:00

  • Genetic basis for chamber-specific ventricular phenotypes in the rat infarct model.

    abstract:BACKGROUND:We, and others, have previously reported a strong correlation between increased inter-ventricular dispersion of repolarization and the occurrence of fatal arrhythmia in animal models of CHF. The existence of this and other such distinct electrophysiologic phenotypes in right (RV) vs. left ventricles (LV) cou...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00703-4

    authors: Chugh SS,Whitesel S,Turner M,Roberts CT Jr,Nagalla SR

    更新日期:2003-02-01 00:00:00

  • Sarcoplasmic reticulum Ca2+-ATPase modulates cardiac contraction and relaxation.

    abstract::The cardiac SR Ca(2+)-ATPase (SERCA2a) regulates intracellular Ca(2+)-handling and thus, plays a crucial role in initiating cardiac contraction and relaxation. SERCA2a may be modulated through its accessory phosphoprotein phospholamban or by direct phosphorylation through Ca(2+)/calmodulin dependent protein kinase II ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1016/s0008-6363(02)00694-6

    authors: Frank KF,Bölck B,Erdmann E,Schwinger RH

    更新日期:2003-01-01 00:00:00

  • Exercise training prevents ventricular tachycardia in CPVT1 due to reduced CaMKII-dependent arrhythmogenic Ca2+ release.

    abstract:AIMS:Catecholaminergic polymorphic ventricular tachycardia type 1 (CPVT1) is caused by mutations in the cardiac ryanodine receptor (RyR2) that lead to disrupted Ca(2+) handling in cardiomyocytes and ventricular tachycardia. The aim of this study was to test whether exercise training could reduce the propensity for arrh...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvw095

    authors: Manotheepan R,Danielsen TK,Sadredini M,Anderson ME,Carlson CR,Lehnart SE,Sjaastad I,Stokke MK

    更新日期:2016-08-01 00:00:00

  • The angiotensin II type 2 receptor activates flow-mediated outward remodelling through T cells-dependent interleukin-17 production.

    abstract:AIMS:The angiotensin II type 1 receptor (AT1R) through the activation of immune cells plays a key role in arterial inward remodelling and reduced blood flow in cardiovascular disorders. On the other side, flow (shear stress)-mediated outward remodelling (FMR), involved in collateral arteries growth in ischaemic disease...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvw172

    authors: Caillon A,Grenier C,Grimaud L,Vessieres E,Guihot AL,Blanchard S,Lelievre E,Chabbert M,Foucher ED,Jeannin P,Beauvillain C,Abraham P,Loufrani L,Delneste Y,Henrion D

    更新日期:2016-10-01 00:00:00

  • Glucose-induced endothelial heparanase secretion requires cortical and stress actin reorganization.

    abstract:AIMS:Heparanase, which specifically cleaves carbohydrate chains of heparan sulfate, has been implicated in the pathology of diabetes-associated complications. Using high glucose (HG) to replicate hyperglycaemia observed following diabetes, the present study was designed to determine the mechanism by which HG initiates ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvq051

    authors: Wang F,Wang Y,Kim MS,Puthanveetil P,Ghosh S,Luciani DS,Johnson JD,Abrahani A,Rodrigues B

    更新日期:2010-07-01 00:00:00

  • Adenovirus-mediated expression of p35 prevents hypoxia/reoxygenation injury by reducing reactive oxygen species and caspase activity.

    abstract:OBJECTIVE:This study aimed to examine the effects of adenovirus-mediated expression of p35, a baculovirus gene, on apoptosis induced by hypoxia/reoxygenation (H/R) in cardiomyocytes. METHODS:Neonatal rat cardiomyocytes were infected with recombinant adenoviral vectors expressing p35 (Ad2/CMVp35) or no transgene (Ad2/C...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(02)00412-1

    authors: Date T,Belanger AJ,Mochizuki S,Sullivan JA,Liu LX,Scaria A,Cheng SH,Gregory RJ,Jiang C

    更新日期:2002-08-01 00:00:00

  • PEDF induces p53-mediated apoptosis through PPAR gamma signaling in human umbilical vein endothelial cells.

    abstract:OBJECTIVE:Pigment epithelial-derived factor (PEDF) is a potent anti-angiogenic factor whose effects are partially mediated through the induction of endothelial cell apoptosis. The pathway mediating endothelial cell apoptosis has not been fully established. Here we investigated the participation of peroxisome proliferat...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2007.06.032

    authors: Ho TC,Chen SL,Yang YC,Liao CL,Cheng HC,Tsao YP

    更新日期:2007-11-01 00:00:00

  • Enhanced heterogeneity of myocardial conduction and severe cardiac electrical instability in annexin A7-deficient mice.

    abstract:OBJECTIVES:Annexin A7 is involved in cardiomyocyte membrane organization and Ca(2+)-dependent signalling processes. We investigated the impact of annexin A7 on cardiac electrophysiological properties using an annexin A7-deficient mouse strain (annexin A7(-/-)). METHODS:Nineteen adult annexin A7(-/-) and 14 wild-type m...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/j.cardiores.2007.07.001

    authors: Schrickel JW,Brixius K,Herr C,Clemen CS,Sasse P,Reetz K,Grohé C,Meyer R,Tiemann K,Schröder R,Bloch W,Nickenig G,Fleischmann BK,Noegel AA,Schwinger RH,Lewalter T

    更新日期:2007-11-01 00:00:00

  • Interaction between cholinergic and nitrergic vasodilation: a novel mechanism of blood pressure control.

    abstract:OBJECTIVE:Cholinergic vasodilation has been thought to play little if any role in the regulation of blood pressure in humans. Autonomic denervation potentiates the vasoconstriction evoked by nitric oxide synthase inhibition in humans, but the mechanism is unclear. We hypothesized that this may be related to loss of neu...

    journal_title:Cardiovascular research

    pub_type: 临床试验,杂志文章

    doi:10.1016/s0008-6363(01)00325-x

    authors: Lepori M,Sartori C,Duplain H,Nicod P,Scherrer U

    更新日期:2001-09-01 00:00:00

  • Vascularizing the heart.

    abstract::As the developing heart grows and the chamber walls thicken, passive diffusion of oxygen and nutrients is replaced by a vascular plexus which remodels and expands to form a mature coronary vascular system. The coronary arteries and veins ensure the continued development of the heart and facilitate cardiac output with ...

    journal_title:Cardiovascular research

    pub_type: 杂志文章,评审

    doi:10.1093/cvr/cvr035

    authors: Riley PR,Smart N

    更新日期:2011-07-15 00:00:00

  • Cardioprotection with adenosine metabolism inhibitors in ischemic-reperfused mouse heart.

    abstract:OBJECTIVES:To characterize the 'anti-ischemic' effects of adenosine metabolism inhibition in ischemic-reperfused myocardium. METHODS:Perfused C57/B16 mouse hearts were subjected to 20 min ischemia 40 min reperfusion in the absence or presence of adenosine deaminase inhibition (50 microM erythro-2-(2-hydroxy-3-nonyl)ad...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(01)00360-1

    authors: Peart J,Matherne GP,Cerniway RJ,Headrick JP

    更新日期:2001-10-01 00:00:00

  • TNF-α-mediated caspase-8 activation induces ROS production and TRPM2 activation in adult ventricular myocytes.

    abstract:AIMS:TRPM2 is a Ca(2+)-permeable cationic channel of the transient receptor potential (TRP) superfamily that is linked to apoptotic signalling. Its involvement in cardiac pathophysiology is unknown. The aim of this study was to determine whether the pro-apoptotic cytokine tumour necrosis factor-α (TNF-α) induces a TRPM...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1093/cvr/cvu112

    authors: Roberge S,Roussel J,Andersson DC,Meli AC,Vidal B,Blandel F,Lanner JT,Le Guennec JY,Katz A,Westerblad H,Lacampagne A,Fauconnier J

    更新日期:2014-07-01 00:00:00

  • Effect of ischaemic preconditioning on vascular dysfunction induced by ischaemia and reperfusion in rat hindquarters.

    abstract:OBJECTIVE:The aim of this study was to examine the effect of ischaemia on vascular responses to endothelium-dependent and endothelium-independent vasodilators and on vasoconstrictor responses. Furthermore, the ability of preconditioning to prevent ischaemia-induced changes in vascular reactivity was examined in the rat...

    journal_title:Cardiovascular research

    pub_type: 杂志文章

    doi:10.1016/s0008-6363(96)00167-8

    authors: Loke KE,Woodman OL

    更新日期:1996-12-01 00:00:00