Abstract:
Aims:Endothelial hyperpermeability exacerbates multiple organ damage during inflammation or infection. The endothelial glycocalyx, a protective matrix covering the luminal surface of endothelial cells (ECs), undergoes enzymatic shedding during inflammation, contributing to barrier hyperpermeability. A disintegrin and metalloproteinase 15 (ADAM15) is a sheddase capable of cleaving the ectodomains of membrane-bound molecules. Herein, we tested whether and how ADAM15 is involved in glycocalyx shedding and vascular leakage during sepsis. Methods and results:Dextran-150kD exclusion assay revealed lipopolysaccharide (LPS) significantly reduced glycocalyx thickness in mouse cremaster microvessels. Consistently, shedding products of glycocalyx constituents, including CD44 ectodomain, were detected with an increased plasma level after cecal ligation and puncture (CLP)-induced sepsis. The direct effects of CD44 ectodomain on endothelial barrier function were evaluated, which revealed CD44 ectodomain dose-dependently reduced transendothelial electrical resistance (TER) and caused cell-cell adherens junction disorganization. Furthermore, we examined the role of ADAM15 in CD44 cleavage and glycocalyx shedding. An in vitro cleavage assay coupled with liquid chromatography-tandem mass spectrometry confirmed ADAM15 cleaved CD44 at His235-Thr236 bond. In ECs with ADAM15 knockdown, LPS-induced CD44 cleavage and TER reduction were greatly attenuated, whereas, ADAM15 overexpression exacerbated CD44 cleavage and TER response to LPS. Consistently, ADAM15 knockout in mice attenuated CLP-induced increase in plasma CD44. Intravital and electron microscopic images revealed ADAM15 deficiency prevented LPS-induced glycocalyx injury in cremaster and pulmonary microvasculatures. Functionally, ADAM15-/- mice with better-preserved glycocalyx exhibited resistance to LPS-induced vascular leakage, as evidenced by reduced albumin extravasation in pulmonary and mesenteric vessels. Importantly, in intact, functionally vital human lungs, perfusion of LPS induced a significant up-regulation of ADAM15, accompanied by elevated CD44 in the effluent and increased vascular permeability to albumin. Conclusion:Together, our data support the critical role of ADAM15 in mediating vascular barrier dysfunction during inflammation. Its mechanisms of action involve CD44 shedding and endothelial glycocalyx injury.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Yang X,Meegan JE,Jannaway M,Coleman DC,Yuan SYdoi
10.1093/cvr/cvy167subject
Has Abstractpub_date
2018-11-01 00:00:00pages
1752-1763issue
13eissn
0008-6363issn
1755-3245pii
5043287journal_volume
114pub_type
杂志文章abstract:AIMS:Pulmonary hypertension (PH) is a devastating condition for which no disease-modifying therapies exist. PH is recognized as proliferative disease of the pulmonary artery (PA). In the experimental newborn calf model of hypoxia-induced PH, adventitial fibroblasts in the PA wall exhibit a heightened replication index....
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvs194
更新日期:2012-08-01 00:00:00
abstract:OBJECTIVE:The aims of the study were to determine the effect of chronic pressure overload of the left ventricle on the density and distribution of neuropeptide-Y-like immunoreactive (NPY-LI) nerve fibres in heart and to compare any changes to those observed in adrenergic nerve fibres, identified by dopamine beta-hydrox...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.3.494
更新日期:1993-03-01 00:00:00
abstract:OBJECTIVE:Polymorphic ventricular tachycardias (PVT) occur spontaneously in canine hearts under the combination of D-sotalol (S), bradycardia and phenylephrine (PE). We investigated the hypotheses that: (1) the activation patterns of the initial PVT beats would be consistent with an origin in the ventricular conduction...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00036-4
更新日期:1998-06-01 00:00:00
abstract:AIMS:Atrial fibrillation (AF) is a major risk factor for cardio-embolic stroke. Anticoagulant drugs are effective in preventing AF-related stroke. However, the high frequency of anticoagulant-associated major bleeding is a major concern. This study sought to identify new targets to develop safer antithrombotic therapie...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvw049
更新日期:2016-06-01 00:00:00
abstract:AIMS:Atherogenesis, evolution of plaque, and outcomes following endovascular intervention depend heavily on the unique vascular architecture of each individual. Patient-specific, multiscale models able to correlate changes in microscopic cellular responses with relevant macroscopic flow, and structural conditions may h...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvu124
更新日期:2014-07-01 00:00:00
abstract::Currently, a high carbohydrate/low fat diet is recommended for patients with hypertension; however, the potentially important role that the composition of dietary fat and carbohydrate plays in hypertension and the development of pathological left ventricular hypertrophy (LVH) has not been well characterized. Recent st...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.11.007
更新日期:2007-01-15 00:00:00
abstract:OBJECTIVE:Infusion of angiotensin II (AngII) during the third and fourth week after balloon injury of the left common carotid artery of the rat induces smooth muscle cell (SMC) DNA synthesis. In this study we wanted to investigate whether alpha 1-adrenoreceptors are involved in AngII-induced SMC DNA synthesis in the ne...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/0008-6363(95)00216-2
更新日期:1996-02-01 00:00:00
abstract::The effect of chronic propranolol administration (2 mg.kg-1.d-1 for 14d) and withdrawal on microvascular perfusion was studied in rabbit myocardium. Fluorescein isothiocyanate-dextran was injected into four groups of anaesthetised open chest rabbits. Fluorescent microscopy was used to identify the perfused vessels and...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.11.793
更新日期:1988-11-01 00:00:00
abstract:OBJECTIVE:The aim was to examine ventricular brain natriuretic peptide (B-type natriuretic peptide, BNP) gene expression and to determine its relationship with ventricular BNP and circulating BNP levels in paediatric cardiac transplant recipients, over a three year period after transplantation. METHODS:Total RNA extra...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/27.12.2135
更新日期:1993-12-01 00:00:00
abstract:OBJECTIVE:Rapid ventricular pacing reliably induces severe congestive heart failure in dogs, with an associated attenuation of baroreflex sensitivity. Unique to this model is the capacity for rapid recovery of haemodynamics and plasma noradrenaline following the cessation of pacing; however, whether baroreflex sensitiv...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.3.384
更新日期:1994-03-01 00:00:00
abstract:AIMS:Imbalance between pro- and antioxidant species (e.g. during aging) plays a crucial role for vascular function and is associated with oxidative gene regulation and modification. Vascular aging is associated with progressive deterioration of vascular homeostasis leading to reduced relaxation, hypertrophy, and a high...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvn182
更新日期:2008-11-01 00:00:00
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:OBJECTIVE:Cardiac parasympathetic nerve activity is reduced in most cardiovascular disease states, and this may contribute to enhanced cardiac sympathetic responsiveness. Disruption of inhibitory G-proteins (Gi) ablates the cholinergic pathway and increases cardiac endothelial nitric oxide (NO) synthase (eNOS) expressi...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.04.034
更新日期:2005-09-01 00:00:00
abstract::Electrophysiologic remodeling is a process whereby heart disease alters the electrophysiologic properties of cardiac tissue. These alterations, in turn, can cause or exacerbate disease-related arrhythmias. Ion channels are the fundamental molecular units underlying cardiac electrophysiology, and it therefore follows t...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/s0008-6363(99)00063-2
更新日期:1999-05-01 00:00:00
abstract:OBJECTIVES:Saphenous vein graft failures, resulting from thrombosis and the abnormal proliferation, migration and apoptosis of vascular smooth muscle cells (VSMC) are major limitations of coronary artery bypass surgery. We investigated whether surgical trauma of human saphenous vein induces the early response gene c-fo...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00220-5
更新日期:1999-11-01 00:00:00
abstract:OBJECTIVE:Persistent atrial fibrillation (AF) results in an impairment of atrial function. In order to elucidate the mechanism behind this phenomenon, we investigated the gene expression of proteins influencing calcium handling. METHODS:Right atrial appendages were obtained from eight patients with paroxysmal AF, ten ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00045-0
更新日期:1999-05-01 00:00:00
abstract:AIMS:To compare the prevalence of electrocardiogram (ECG)-documented atrial fibrillation (or flutter) (AF) across eight regions of the world, and to examine anti-thrombotic use and clinical outcomes. METHODS AND RESULTS:Baseline ECGs were collected in 153,152 middle-aged participants (ages 35 to 70 years) to document ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa241
更新日期:2020-08-10 00:00:00
abstract:OBJECTIVE:Vascular endothelial growth factor (VEGF), secreted by vascular cells and a variety of tumour cells, is a potent angiogenic factor. Since nitric oxide (NO) seems to play a key role in the VEGF-induced proliferation of endothelial cells, the aim of the present study was to determine whether VEGF stimulates end...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(98)00228-4
更新日期:1999-03-01 00:00:00
abstract:OBJECTIVE:We investigated the influence of experimental hyperlipidemia on the formation of cardiac NO, superoxide, and peroxynitrite (ONOO(-)) in rat hearts. METHODS:Wistar rats were fed 2% cholesterol-enriched diet or normal diet for 8 weeks. Separate groups of normal and hyperlipidemic rats were injected twice intra...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00330-4
更新日期:2003-06-01 00:00:00
abstract::The importance of the vascular adventitia is increasingly being recognized not only in vascular disease but also in normal maintenance and homeostasis of vessels. Activation of the adventitia and its resident fibrocytic cells in response to injury, stretch, cytokines, and hormones has been shown to stimulate different...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2007.06.016
更新日期:2007-09-01 00:00:00
abstract:OBJECTIVE:Lipoprotein lipase (LPL) mediated hydrolysis of circulating triglyceride (TG)-rich lipoproteins provides the heart with fatty acids. The present study was designed to investigate the influence of circulating TG and their lipolysis in facilitating translocation of LPL from the underlying cardiomyocyte cell sur...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00469-3
更新日期:2003-09-01 00:00:00
abstract:OBJECTIVE:The aim was to examine the effect of doxorubicin on spontaneous cyclic Ca2+ release from the sarcoplasmic reticulum of skinned fibres, as measured by isometric tension development in EGTA free, Ca2+ free solution. METHODS:Experiments were done on fragments of papillary muscles from the right ventricles of gu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/26.4.371
更新日期:1992-04-01 00:00:00
abstract::Although the level and pace of population aging display high geographical variability, virtually all countries have been experiencing growth in their elderly population, particularly in developed nations. Because aging is a major risk factor for atherosclerosis and associated disease, it is of up most importance to un...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2004.09.007
更新日期:2005-05-01 00:00:00
abstract::Muscle tissue in atrioventricular (A-V) cardiac valve leaflets was studied in 35 human hearts and was found to be more prominent in the anterior leaflet of the mitral (MAL) than in the other valve leaflets. From serial sectioning and wax model reconstruction, the anatomic arrangement of the muscle in the MAL indicates...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/12.11.675
更新日期:1978-11-01 00:00:00
abstract:AIMS:The effects of serelaxin, a recombinant form of human relaxin-2 peptide, on vascular function in the coronary microvascular and systemic macrovascular circulation remain largely unknown. This mechanistic, clinical study assessed the effects of serelaxin on myocardial perfusion, aortic stiffness, and safety in pati...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz345
更新日期:2021-01-01 00:00:00
abstract:OBJECTIVE:Automatic analysis of the frequency content of the fibrillatory baseline on the surface ECG accurately reflects the average rate of atrial fibrillation (AF). This frequency measurement correlates with the behavior of AF and predicts the response to administration of ibutilide, a new antiarrhythmic drug. Neith...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00156-x
更新日期:1999-10-01 00:00:00
abstract:AIMS:Regional heterogeneities in contraction contribute to heart failure with reduced ejection fraction (HFrEF). We aimed to determine whether regional changes in myocardial relaxation similarly contribute to diastolic dysfunction in post-infarction HFrEF, and to elucidate the underlying mechanisms. METHODS AND RESULT...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy257
更新日期:2019-03-15 00:00:00
abstract:OBJECTIVE:The aim was to investigate how platelet activation during myocardial ischaemia can induce electrophysiological and arrhythmogenic effects, and examine the involvement of different platelet membrane receptors in producing these effects. METHODS:Transmembrane action potentials and electrograms were recorded fr...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/28.11.1662
更新日期:1994-11-01 00:00:00
abstract:Aims:Chronic heart failure is becoming increasingly prevalent and is still associated with a high mortality rate. Myocardial hypertrophy and fibrosis drive cardiac remodelling and heart failure, but they are not sufficiently inhibited by current treatment strategies. Furthermore, despite increasing knowledge on cardiom...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy154
更新日期:2019-01-01 00:00:00
abstract:AIMS:The expression of PUMA (p53-up-regulated modulator of apoptosis), an apoptosis-regulating gene, increases during endoplasmic reticulum stress. The mechanisms by which cyclic stretch influences the regulation of PUMA in vascular smooth muscle cells (VSMCs) during apoptosis remain unclear. We hypothesized that cycli...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvr280
更新日期:2012-01-01 00:00:00