Abstract:
AIMS:Processes in the development of atherosclerotic lesions can lead to plaque rupture or erosion, which can in turn elicit myocardial infarction or ischaemic stroke. The aims of this study were to determine whether Toll-like receptor 7 (TLR7) gene expression levels influence patient outcome and to explore the mechanisms linked to TLR7 expression in atherosclerosis. METHODS AND RESULTS:Atherosclerotic plaques were removed by carotid endarterectomy (CEA) and subjected to gene array expression analysis (n = 123). Increased levels of TLR7 transcript in the plaques were associated with better outcome in a follow-up study over a maximum of 8 years. Patients with higher TLR7 transcript levels had a lower risk of experiencing major cardiovascular and cerebrovascular events (MACCE) during the follow-up period after CEA (hazard ratio: 2.38, P = 0.012, 95% CI 1.21-4.67). TLR7 was expressed in all plaques by T cells, macrophages and endothelial cells in capillaries, as shown by immunohistochemistry. In short-term tissue cultures, ex vivo treatment of plaques with the TLR7 ligand imiquimod elicited dose-dependent secretion of IL-10, TNF-α, GM-CSF, and IL-12/IL-23p40. This secretion was blocked with a TLR7 inhibitor. Immunofluorescent tissue analysis after TLR7 stimulation showed IL-10 expression in T cells, macrophages and vascular smooth muscle cells. TLR7 mRNA levels in the plaques were correlated with IL-10 receptor (r = 0.4031, P < 0.0001) and GM-CSF receptor A (r = 0.4354, P < 0.0001) transcripts. CONCLUSION:These findings demonstrate that TLR7 is abundantly expressed in human atherosclerotic plaques. TLR7 ligation elicits the secretion of pro-inflammatory and anti-inflammatory cytokines, and high TLR7 expression in plaques is associated with better patient outcome, suggesting that TLR7 is a potential therapeutic target for prevention of complications of atherosclerosis.
journal_name
Cardiovasc Resjournal_title
Cardiovascular researchauthors
Karadimou G,Folkersen L,Berg M,Perisic L,Discacciati A,Roy J,Hansson GK,Persson J,Paulsson-Berne Gdoi
10.1093/cvr/cvw231subject
Has Abstractpub_date
2017-01-01 00:00:00pages
30-39issue
1eissn
0008-6363issn
1755-3245pii
cvw231journal_volume
113pub_type
杂志文章abstract::Peptidyl-prolyl cis-trans-isomerases are a highly conserved family of immunophilins. The three peptidyl-prolyl cis-trans-isomerase subfamilies are cyclophilins, FK-506-binding proteins, and parvulins. Peptidyl-prolyl cis-trans-isomerases are expressed in multiple human tissues and regulate different cellular functions...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvv096
更新日期:2015-06-01 00:00:00
abstract:OBJECTIVE:It has been proposed that human immunodeficiency virus (HIV) infection-induced inflammatory environment may contribute to the pathogenesis of cardiovascular diseases. Recent studies have also demonstrated the potential role of estrogen as therapeutic agents in the prevention or treatment of cardiovascular dis...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.03.006
更新日期:2004-07-01 00:00:00
abstract:OBJECTIVE:Hereditary long QT syndrome (LQTS) is a genetically heterogeneous disease characterized by prolonged QT intervals and an increased risk for ventricular arrhythmias and sudden cardiac death. Mutations in the voltage-gated potassium channel subunit KCNQ1 induce the most common form of LQTS. KCNQ1 is associated ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2005.05.003
更新日期:2005-08-15 00:00:00
abstract:AIMS:Atrial fibrillation (AF) is the most common cardiac arrhythmia, and early-onset lone AF has been linked to mutations in genes encoding ion channels. Mutations in the pore forming subunit KV4.3 leading to an increase in the transient outward potassium current (Ito) have previously been associated with the Brugada S...
journal_title:Cardiovascular research
pub_type: 杂志文章,多中心研究
doi:10.1093/cvr/cvt028
更新日期:2013-06-01 00:00:00
abstract:OBJECTIVE:The purpose of this study was to determine whether exercise training could precondition the myocardium against hydrogen peroxide (H(2)O(2))-induced damage. METHODS:Male Fischer 344 rats ran on a treadmill for 9 weeks (60 min/day, 22 m/min, 6 degrees grade, 5 days/week). Isolated perfused working hearts from ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(03)00285-2
更新日期:2003-06-01 00:00:00
abstract:OBJECTIVES:While it is probable that the cerebrovascular spasm which occurs after subarachnoid haemorrhage results from the action of haemoglobin, the mechanism of that process remains unclear. These studies were thus designed to test the hypothesis that the action of oxyhaemoglobin results from the iron-catalyzed form...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1995-10-01 00:00:00
abstract::The effects of hypoxia and subsequent reoxygenation were examined in isolated left ventricular papillary muscles from the rat at 28 degrees C and 33 degrees C. Studies of relaxation were carried out in isometric and physiologically sequenced contractions. In studies of isometric contractions, the following variables w...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/20.9.690
更新日期:1986-09-01 00:00:00
abstract:OBJECTIVE:The adhesive interaction of monocytes and endothelial cells has been implicated as a regulatory signal in the cell activation that is involved in the pathogenesis of atherosclerosis. We investigated the effect of monocyte-endothelial cell interaction on the expression of adhesion molecules, intercellular adhe...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/0008-6363(96)00085-5
更新日期:1996-08-01 00:00:00
abstract::End tidal PCO2 (PETCO2) has been found to be a good prognostic indicator of successful resuscitation from cardiac arrest. To explore the value of this measurement further, we carried out a series of experiments during cardiac arrest and closed chest resuscitation in 14 mechanically ventilated Sprague-Dawley rats. Vent...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/23.4.364
更新日期:1989-04-01 00:00:00
abstract:OBJECTIVE:Lower limb perfusion following arterial occlusion depends on the recruitment of collateral vessels. Blood flow through these collateral vessels may be jeopardized by hypersensitivity to vasoconstriction by serotonin (5-HT), as has been reported during hyperlipidemia and diabetes. Therefore the aim of this stu...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00538-2
更新日期:2002-11-01 00:00:00
abstract:OBJECTIVE AND METHODS:In this study, we investigated whether Ca(2+) transients are altered in Purkinje cell aggregates dispersed from the subendocardium overlying the infarcted zone of the left ventricle (IZPCs) 48 h after coronary artery occlusion. To do so, we combined epifluorescent imaging with microelectrode recor...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(02)00725-3
更新日期:2003-03-01 00:00:00
abstract:AIMS:Fibromuscular dysplasia (FMD) and spontaneous coronary artery dissection (SCAD) are related, non-atherosclerotic arterial diseases mainly affecting middle-aged women. Little is known about their physiopathological mechanisms. We aimed to identify rare genetic causes to elucidate molecular mechanisms implicated in ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvaa161
更新日期:2020-06-12 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:AIMS:Sleep disturbances exhibit a strong social patterning, and inadequate sleep has been associated with adverse health outcomes, including cardiovascular disorders (CVD). However, the contribution of sleep to socioeconomic inequalities in CVD is unclear. This study pools data from eight European cohorts to investigat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvz267
更新日期:2020-07-01 00:00:00
abstract::Blood vessels are permanently exposed to stretch and shear stress due to blood pressure and blood flow. Significant variations in the mechanical environment, of physiological or pathophysiological nature, occur in vivo. These trigger acute changes in vessel diameter that tend to restore basal levels of tensile and she...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1016/j.cardiores.2006.05.008
更新日期:2006-07-15 00:00:00
abstract:OBJECTIVE:Heme oxygenases (HO) are the rate-limiting enzymes in heme degradation, catalyzing the breakdown of heme to equimolar quantities of biliverdin (BV), carbon monoxide (CO), and ferrous iron. The inducible HO isoform, HO-1, confers protection against ischemia/reperfusion (I/R)-injury in the heart. We hypothesize...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2004.04.015
更新日期:2004-08-15 00:00:00
abstract:AIMS:Doxorubicin (DOX) is a widely used and effective anti-cancer therapeutic. DOX treatment is associated with both acute and late onset cardiotoxicity, limiting its overall efficacy. Here, the impact of cardiomyocyte cell cycle activation was examined in a juvenile model featuring aspects of acute and late onset DOX ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvy273
更新日期:2019-04-15 00:00:00
abstract::The effects of increasing oxygen tension from fetal to neonatal levels and of incubation in the cyclo-oxygenase inhibitor, indomethacin, on the response of isolated rings of neonatal rabbit ductus arteriosus and aorta to noradrenaline were studied in vitro. Increasing oxygen tension did not affect the sensitivity, as ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.12.910
更新日期:1988-12-01 00:00:00
abstract:AIMS:The heart contains c-kit(+) progenitors that maintain cardiac homeostasis. Cardiac c-kit(+) cells are multipotent and give rise to myocardial, endothelial and smooth muscle cells, both in vitro and in vivo. C-kit(+) cells have been thoroughly investigated for their stem cell activity, susceptibility to stress cond...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvq292
更新日期:2011-02-01 00:00:00
abstract:OBJECTIVE:Macrophage migration inhibitory factor (MIF), which plays a pivotal role in the control of inflammatory responses, was first characterized as a T-cell cytokine, but later was also found as a pituitary peptide released in response to infection and stress. However, MIF's role and expression in the myocardium ha...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(01)00408-4
更新日期:2001-12-01 00:00:00
abstract::Segments of the canine ascending aorta, upper descending thoracic aorta, and middle descending thoracic aorta were instrumented with ultrasonic dimension gauges and a cathetertip manometer simultaneously to measure changes in segment diameter, length, and intravascular pressure. Volume distensibility (EV) was calculat...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/22.6.385
更新日期:1988-06-01 00:00:00
abstract:OBJECTIVE:The acute administration of growth hormone (GH) or insulin-like growth factor-1 (IGF-1) improves cardiac performance, possibly contributing to the beneficial effects of GH therapy on heart failure (HF). GH can induce the production of IGF-1 and thus the actions of GH may be mediated through its IGF-1 inductio...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00058-9
更新日期:1999-07-01 00:00:00
abstract:OBJECTIVES:Prior studies have shown that the performance of the left ventricle on any one beat is influenced by the mechanical events of the previous beat, a phenomenon called "previous-beat contraction history". This previous-beat contraction history, which appears to be an interplay between the mechanical events of o...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-07-01 00:00:00
abstract:OBJECTIVE:The aim of this study is to investigate the idea that altered fibroblast contractile activity is involved in the pathogenesis of hypertensive heart disease (HHD). METHODS:Cell area and contraction are quantified using the traction force microscopy technique for cardiac fibroblasts isolated from both normoten...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/j.cardiores.2003.09.021
更新日期:2003-12-01 00:00:00
abstract:OBJECTIVES:Collagen synthesis is one of the major mechanisms of primary atherosclerotic plaque growth and is likely to be similarly important in restenosis. The patterns of collagen gene expression in human restenosis and associations with thrombosis/hemorrhage have not been described. METHODS:Using human coronary art...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:
更新日期:1996-09-01 00:00:00
abstract::Atrial fibrillation (AF) is the most common tachyarrhythmia in clinical practice. Over decades of research, a vast amount of knowledge has been gathered about the causes and consequences of AF related to cellular electrophysiology and features of the tissue structure that influence the propagation of fibrillation wave...
journal_title:Cardiovascular research
pub_type: 杂志文章,评审
doi:10.1093/cvr/cvw007
更新日期:2016-04-01 00:00:00
abstract::The effects of both gradual and abrupt coronary occlusion on regional wall function (sonomicrometry) and left ventricular relaxation were studied in the intact dog heart. The ischaemic dysfunction observed in the two interventions as assessed by pressure-length loops showed considerably different patterns. The regiona...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/21.7.507
更新日期:1987-07-01 00:00:00
abstract:AIMS:Extracellular nucleotides are vasoactive molecules. The concentrations of these molecules are regulated by ectonucleotidases. In this study, we investigated the role of the blood vessel ectonucleotidase NTPDase1, in the vasoconstrictor effect of nucleotides using Entpd1(-/-) mice. METHODS AND RESULTS:Immunofluore...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/cvp265
更新日期:2010-01-01 00:00:00
abstract:OBJECTIVES:The contribution of vascular changes to the development of heart failure is largely unknown. In the present study, we evaluated endothelial and vascular contractile function in the rat hindlimb vascular bed after myocardial infarction (MI), including the modulatory role of basal nitric oxide (NO) production ...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1016/s0008-6363(99)00147-9
更新日期:1999-08-15 00:00:00
abstract::Regional myocardial anoxia was produced in dogs by perfusion of the left circumflex artery (LCA) with deoxygenated blood. Isolated sarcoplasmic reticulum fragments (cardiac relaxing system) showed decreased Ca2+ binding and uptake. The ability of isolated mitochondria to utilise long-chain fatty acids was markedly red...
journal_title:Cardiovascular research
pub_type: 杂志文章
doi:10.1093/cvr/11.6.568
更新日期:1977-11-01 00:00:00