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 Resjournal_title
Cardiovascular researchauthors
Hollier PL,Chapouly C,Diop A,Guimbal S,Cornuault L,Gadeau AP,Renault MAdoi
10.1093/cvr/cvaa285subject
Has Abstractpub_date
2020-10-16 00:00:00eissn
0008-6363issn
1755-3245pii
5924557pub_type
杂志文章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
更新日期:2003-11-01 00:00:00
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
更新日期:2013-02-01 00:00:00
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
更新日期:2018-03-15 00:00:00
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
更新日期:2005-02-01 00:00:00
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
更新日期:2002-04-01 00:00:00
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
更新日期:2020-05-01 00:00:00
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
更新日期:2009-07-15 00:00:00
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
更新日期:2020-03-01 00:00:00
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
更新日期:2002-08-15 00:00:00
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
更新日期:2004-02-15 00:00:00
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
更新日期:1990-09-01 00:00:00
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
更新日期:2001-01-01 00:00:00
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
更新日期:1993-02-01 00:00:00
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
更新日期:1985-05-01 00:00:00
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
更新日期:1979-05-01 00:00:00
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
更新日期:2000-09-01 00:00:00
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
更新日期:1980-05-01 00:00:00
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
更新日期:2003-02-01 00:00:00
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
更新日期:2003-01-01 00:00:00
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
更新日期:2016-08-01 00:00:00
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
更新日期:2016-10-01 00:00:00
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
更新日期:2010-07-01 00:00:00
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
更新日期:2002-08-01 00:00:00
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
更新日期:2007-11-01 00:00:00
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
更新日期:2007-11-01 00:00:00
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
更新日期:2001-09-01 00:00:00
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
更新日期:2011-07-15 00:00:00
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
更新日期:2001-10-01 00:00:00
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
更新日期:2014-07-01 00:00:00
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
更新日期:1996-12-01 00:00:00