Abstract:
AIMS:Collagen degradation in atherosclerotic plaques with thin fibrous caps renders them more prone to rupture. Fibroblast activation protein (FAP) plays a role in arthritis and tumour formation through its collagenase activity. However, the significance of FAP in thin-cap human fibroatheromata remains unknown. METHODS AND RESULTS:We detected enhanced FAP expression in type IV-V human aortic atheromata (n = 12), compared with type II-III lesions (n = 9; P < 0.01) and healthy aortae (n = 8; P < 0.01) by immunostaining and western blot analyses. Fibroblast activation protein was also increased in thin-cap (<65 µm) vs. thick-cap (≥ 65 µm) human coronary fibroatheromata (n = 12; P < 0.01). Fibroblast activation protein was expressed by human aortic smooth muscle cells (HASMC) as shown by colocalization on immunofluorescent aortic plaque stainings (n = 10; P < 0.01) and by flow cytometry in cell culture. Although macrophages did not express FAP, macrophage burden in human aortic plaques correlated with FAP expression (n = 12; R(2)= 0.763; P < 0.05). Enzyme-linked immunosorbent assays showed a time- and dose-dependent up-regulation of FAP in response to human tumour necrosis factor α (TNFα) in HASMC (n = 6; P < 0.01). Moreover, supernatants from peripheral blood-derived macrophages induced FAP expression in cultured HASMC (n = 6; P < 0.01), an effect abolished by blocking TNFα (n = 6; P < 0.01). Fibroblast activation protein associated with collagen-poor regions in human coronary fibrous caps and digested type I collagen and gelatin in vitro (n = 6; P < 0.01). Zymography revealed that FAP-mediated collagenase activity was neutralized by an antibody directed against the FAP catalytic domain both in HASMC (n = 6; P < 0.01) and in fibrous caps of atherosclerotic plaques (n = 10; P < 0.01). CONCLUSION:Fibroblast activation protein expression in HASMC is induced by macrophage-derived TNFα. Fibroblast activation protein associates with thin-cap human coronary fibroatheromata and contributes to type I collagen breakdown in fibrous caps.
journal_name
Eur Heart Jjournal_title
European heart journalauthors
Brokopp CE,Schoenauer R,Richards P,Bauer S,Lohmann C,Emmert MY,Weber B,Winnik S,Aikawa E,Graves K,Genoni M,Vogt P,Lüscher TF,Renner C,Hoerstrup SP,Matter CMdoi
10.1093/eurheartj/ehq519subject
Has Abstractpub_date
2011-11-01 00:00:00pages
2713-22issue
21eissn
0195-668Xissn
1522-9645pii
ehq519journal_volume
32pub_type
杂志文章abstract::Modern-day stenting procedures leverage advances in pharmacotherapy and device innovation. Patients treated with contemporary antiplatelet agents, peri-procedural antithrombin therapy and new-generation drug-eluting stents (DES) have excellent outcomes over the short to medium term. Indeed, coupled with the reducing c...
journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/ehv511
更新日期:2015-12-14 00:00:00
abstract:AIMS:In animal models of obesity and diabetes mellitus, myocardial TG accumulation is associated with decreased myocardial function. In the physiologically ageing heart, myocardial triglyceride (TG) accumulation may also occur due to reduced myocardial fatty acid oxidation. The role of myocardial TG in the ageing human...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehn207
更新日期:2008-06-01 00:00:00
abstract:AIMS:The association of body weight and weight change with mortality and cardiovascular (CV) outcome in patients with diabetes mellitus (DM) is not clearly established. We assessed the relationship between weight, weight change, and outcomes in patients with established CV risk factors and type 2 DM or pre-diabetes. M...
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abstract::Over two decades after the introduction of cardiac resynchronization therapy (CRT) into clinical practice, ∼30% of candidates continue to fail to respond to this highly effective treatment of drug-refractory heart failure (HF). Since the causes of this non-response (NR) are multifactorial, it will require multidiscipl...
journal_title:European heart journal
pub_type: 杂志文章,评审
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journal_title:European heart journal
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doi:10.1093/eurheartj/ehi351
更新日期:2005-10-01 00:00:00
abstract::Liaison with two important scientific societies in the field of hypertension improves contact with readers. ...
journal_title:European heart journal
pub_type: 新闻
doi:
更新日期:2012-05-01 00:00:00
abstract::For clinical prognosis, LV function is best described in terms of ejection fraction (EF) or end-systolic volume (ESV). Because deterioration of LV function is the most important adverse prognostic factor for patients after recovery from myocardial infarction, any agent which improves function should improve long-term ...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1093/eurheartj/11.suppl_f.5
更新日期:1990-08-01 00:00:00
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更新日期:2006-07-01 00:00:00
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doi:10.1093/eurheartj/eht356
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pub_type: 杂志文章,评审
doi:10.1093/eurheartj/14.suppl_a.33
更新日期:1993-07-01 00:00:00
abstract::Brief hyperventilation is occasionally accompanied by repolarization abnormalities in subjects without apparent heart disease. However, the effect of prolonged hyperventilation on repolarization abnormalities is not clearly defined. We analysed the repolarization abnormalities induced by prolonged hyperventilation, co...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a015079
更新日期:1996-09-01 00:00:00
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journal_title:European heart journal
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更新日期:1992-08-01 00:00:00
abstract::Thrombolytic treatment efficacy is greater when the delay between onset of pain and treatment is short. One way to shorten this delay is to give treatment at home, but one cannot recommend this technique if it has not been demonstrated first, that pre-hospital thrombolysis is feasible and safe, and second, that it is ...
journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1093/eurheartj/11.suppl_f.43
更新日期:1990-08-01 00:00:00
abstract:AIMS:Hypertrophic cardiomyopathy (HCM) is a disease with marked regional differences in wall thickness. However, the relation between myocardial function and wall thickness has not been well studied. Ultrasonic strain rate (SR) imaging makes it possible to study the regional myocardial deformation. We investigated whet...
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doi:10.1093/eurheartj/ehm444
更新日期:2007-12-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a062198
更新日期:1987-11-01 00:00:00
abstract:AIMS:In patients with ischaemic left ventricular (LV) dysfunction and viable myocardium, revascularization improves systolic function. Diastolic dysfunction is also present in such patients; however, whether revascularization improves diastolic function also is largely unknown. METHODS:Twenty-six patients with chronic...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehp125
更新日期:2009-06-01 00:00:00
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doi:10.1093/eurheartj/ehaa756
更新日期:2020-11-26 00:00:00
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更新日期:1995-04-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a060033
更新日期:1992-01-01 00:00:00
abstract::Ambient air pollution is a leading cause of non-communicable disease globally. The largest proportion of deaths and morbidity due to air pollution is now known to be due to cardiovascular disorders. Several particulate and gaseous air pollutants can trigger acute events (e.g. myocardial infarction, stroke, heart failu...
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pub_type: 杂志文章,评审
doi:10.1093/eurheartj/ehy481
更新日期:2018-10-07 00:00:00
abstract:AIMS:To evaluate the effectiveness and safety of bivalirudin as used in routine care. Bivalirudin has been studied as an alternative to heparin plus glycoprotein IIb/IIIa inhibitor (GPI) during percutaneous coronary intervention (PCI). Trials have indicated that bivalirudin is non-inferior to heparin with respect to de...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/eurheartj/ehp437
更新日期:2010-03-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章,meta分析
doi:10.1093/eurheartj/15.suppl_b.9
更新日期:1994-05-01 00:00:00
abstract::The purpose of the study was to determine the sensitivity and specificity of two-dimensional echocardiography (2dE) in the detection of impaired left ventricular function, compared with cineventriculography (CVG). Apical two-dimensional echocardiograms were performed in 110 patients undergoing heart catheterization fo...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a061694
更新日期:1984-06-01 00:00:00
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journal_title:European heart journal
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1053/euhj.2001.2679
更新日期:2001-12-01 00:00:00
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journal_title:European heart journal
pub_type: 杂志文章,评审
doi:10.1093/eurheartj/ehv487
更新日期:2017-03-01 00:00:00
abstract::This case report describes the delayed improvement of left ventricular function by recanalization of an occluded coronary artery in a patient with intractable heart failure and three-vessel disease. The left anterior descending coronary artery was occluded distal to the first septal branch, the dominant right coronary...
journal_title:European heart journal
pub_type: 杂志文章
doi:10.1093/oxfordjournals.eurheartj.a059698
更新日期:1990-03-01 00:00:00