Abstract:
BACKGROUND:Several epidermal growth factor receptor (EGFR) inhibitors have been successfully developed for the treatment of cancer, limiting tumor growth and metastasis. EGFR is also expressed by leukocytes, but little is known about its role in the modulation of the immune response. OBJECTIVES:The aim of this study was to determine whether EGFR expressed on CD4+ T cells is functional and to address the consequences of EGFR inhibition in atherosclerosis, a T cell-mediated vascular chronic inflammatory disease. METHODS:The authors used EGFR tyrosine kinase inhibitors (AG-1478, erlotinib) and chimeric Ldlr-/-Cd4-Cre/Egfrlox/lox mouse with a specific deletion of EGFR in CD4+ T cells. RESULTS:Mouse CD4+ T cells expressed EGFR, and the EGFR tyrosine kinase inhibitor AG-1478 blocked in vitro T cell proliferation and Th1/Th2 cytokine production. In vivo, treatment of Ldlr-/- mice with the EGFR inhibitor erlotinib induced T cell anergy, reduced T cell infiltration within atherosclerotic lesions, and protected against atherosclerosis development and progression. Selective deletion of EGFR in CD4+ T cells resulted in decreased T cell proliferation and activation both in vitro and in vivo, as well as reduced interferon-γ, interleukin-4, and interleukin-2 production. Atherosclerotic lesion size was reduced by 2-fold in irradiated Ldlr-/- mice reconstituted with bone marrow from Cd4-Cre/Egfrlox/lox mice, compared to Cd4-Cre/Egfr+/+ chimeric mice, after 4, 6, and 12 weeks of high-fat diet, associated with marked reduction in T cell infiltration in atherosclerotic plaques. Human blood T cells expressed EGFR and EGFR inhibition reduced T cell proliferation both in vitro and in vivo. CONCLUSIONS:EGFR blockade induced T cell anergy in vitro and in vivo and reduced atherosclerosis development. Targeting EGFR may be a novel strategy to combat atherosclerosis.
journal_name
J Am Coll Cardioljournal_title
Journal of the American College of Cardiologyauthors
Zeboudj L,Maître M,Guyonnet L,Laurans L,Joffre J,Lemarie J,Bourcier S,Nour-Eldine W,Guérin C,Friard J,Wakkach A,Fabre E,Tedgui A,Mallat Z,Tharaux PL,Ait-Oufella Hdoi
10.1016/j.jacc.2017.10.084subject
Has Abstractpub_date
2018-01-16 00:00:00pages
160-172issue
2eissn
0735-1097issn
1558-3597pii
S0735-1097(17)41588-9journal_volume
71pub_type
杂志文章abstract::Intraaortic balloon counterpulsation was instituted in two adult patients whose condition was rapidly deteriorating because of critical decompensated valvular aortic stenosis. The acute hemodynamic effect of counterpulsation in these patients was compared with the effect of counterpulsation in three control patients w...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(85)80399-5
更新日期:1985-03-01 00:00:00
abstract::Fibromuscular dysplasia (FMD) involving the coronary arteries is an uncommon but important condition that can present as acute coronary syndrome, left ventricular dysfunction, or potentially sudden cardiac death. Although the classic angiographic "string of beads" that may be observed in renal artery FMD does not occu...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.jacc.2014.07.014
更新日期:2014-09-09 00:00:00
abstract:OBJECTIVES:This study examined the influence of left ventricular hypertrophy on the accuracy of exercise electrocardiography and echocardiography for detection of coronary artery disease. BACKGROUND:Electrocardiographic repolarization abnormalities caused by left ventricular hypertrophy compromise the diagnostic accur...
journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章
doi:10.1016/0735-1097(96)81472-0
更新日期:1995-11-01 00:00:00
abstract:BACKGROUND:Patients with gout are at an increased risk of cardiovascular (CV) disease including myocardial infarction (MI), stroke, and heart failure (HF). OBJECTIVES:The authors conducted a cohort study to examine comparative CV safety of the 2 gout treatments-probenecid and allopurinol-in patients with gout. METHOD...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2017.12.052
更新日期:2018-03-06 00:00:00
abstract:OBJECTIVES:We tested the feasibility of using analysis of color kinesis images to objectively assess global and regional left ventricular (LV) diastolic function in patients with dilated cardiomyopathy (DCM). In addition, the ability of this technique to track drug-induced changes on LV diastolic properties was studied...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(98)00144-2
更新日期:1998-06-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 临床试验,杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jacc.2003.07.033
更新日期:2004-01-07 00:00:00
abstract:OBJECTIVES:This study investigated whether reduced levels of circulating endothelial progenitors cells (EPCs) in chronic heart failure (CHF) are secondary to an exhaustion of hematopoietic stem cells (HSCs) in the bone marrow or to reduced mobilization. BACKGROUND:Circulating EPCs presumably originate from bone marrow...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2007.01.095
更新日期:2007-06-19 00:00:00
abstract:BACKGROUND:Subclinical inflammation mediated in part by interleukin (IL)-1β participates in peripheral insulin resistance and impaired pancreatic insulin secretion. OBJECTIVES:The authors tested the hypothesis that the IL-1β inhibitor canakinumab reduces incident diabetes. METHODS:The authors randomized 10,061 patien...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jacc.2018.03.002
更新日期:2018-05-29 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
doi:10.1016/j.jacc.2019.10.062
更新日期:2020-03-03 00:00:00
abstract:OBJECTIVES:We sought to test the hypothesis that C-reactive protein, a marker of inflammation, would correlate positively with coronary calcium, a marker of atherosclerosis, in postmenopausal women. BACKGROUND:High sensitivity testing for C-reactive protein (hsCRP) has recently been shown in large population studies t...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(00)00680-x
更新日期:2000-07-01 00:00:00
abstract:OBJECTIVES:This study sought to assess whether baseline and change in contemporary sensitive troponin I (TnI) levels predicts coronary heart disease (CHD) death and myocardial infarction (MI), and to determine the effects of pravastatin on TnI levels. BACKGROUND:The role of troponins in predicting long-term outcomes i...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jacc.2013.08.1643
更新日期:2014-02-04 00:00:00
abstract:BACKGROUND:Exercise has been proposed as a trigger for arrhythmogenic right ventricular cardiomyopathy (ARVC) phenotype manifestation; however, research is hampered by the limited availability of animal models in which disease-associated mutations can be tested. OBJECTIVES:This study evaluated the impact of exercise o...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2015.01.045
更新日期:2015-04-14 00:00:00
abstract:OBJECTIVES:The purpose of this study was to determine whether alterations in cardiac structure or function contribute to the increased risk associated with renal impairment after myocardial infarction (MI). BACKGROUND:Renal impairment is associated with adverse cardiovascular outcomes after MI. METHODS:Echocardiograp...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jacc.2007.06.018
更新日期:2007-09-25 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(98)00379-9
更新日期:1998-11-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(88)90108-8
更新日期:1988-02-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/0735-1097(93)90541-8
更新日期:1993-11-01 00:00:00
abstract::Stroke survivors carry a high risk of recurrence. Antithrombotic medications are paramount for secondary prevention and thus crucial to reduce the overall stroke burden. Appropriate antithrombotic agent selection should be based on the best understanding of the physiopathological mechanism that led to the initial isch...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,评审
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更新日期:2019-08-13 00:00:00
abstract:OBJECTIVE:We sought to evaluate the vena contracta width (VCW) measured using color Doppler as an index of severity of tricuspid regurgitation (TR). BACKGROUND:The VCW is a reliable measure of mitral and aortic regurgitation, but its value in measuring TR is uncertain. METHODS:In 71 consecutive patients with TR, the ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(00)00762-2
更新日期:2000-08-01 00:00:00
abstract:BACKGROUND:Angiotensin-(1-9) [Ang-(1-9)] is a novel peptide of the counter-regulatory axis of the renin-angiotensin-aldosterone system previously demonstrated to have therapeutic potential in hypertensive cardiomyopathy when administered via osmotic mini-pump. Here, we investigate whether gene transfer of Ang-(1-9) is ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2016.09.946
更新日期:2016-12-20 00:00:00
abstract::It has been suggested that intracardiac lymphatics may play a role in the pathophysiologic processes involving the conduction system. To test the possibility of linkage between the ventricular septum and the atrioventricular (AV) node, india ink was injected into the ventricular septum of freshly removed human hearts....
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(83)80114-4
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2012.09.037
更新日期:2013-01-08 00:00:00
abstract:OBJECTIVES:We sought to evaluate the prognostic value of cardiac troponin I (cTnI) in asymptomatic, ambulatory patients with chronic renal failure treated with long-term hemodialysis. BACKGROUND:Smaller, short-term follow-up studies on this subject have given conflicting results. METHODS:A total of 126 ambulatory pat...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(01)01513-3
更新日期:2001-10-01 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2007.09.055
更新日期:2008-02-05 00:00:00
abstract::Myocardial reperfusion after reversible regional ischemia is known to result in delayed recovery of contractile function, but the mechanism responsible for this phenomenon remains unclear. We examined the ability of N-2-mercaptopropionylglycine, a synthetic thiol compound with oxygen free radical scavenging properties...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/s0735-1097(86)80396-5
更新日期:1986-11-01 00:00:00
abstract:OBJECTIVES:The purpose of this study was to characterize patients with mitral regurgitation (MR) and atrial fibrillation (AF) treated percutaneously using the MitraClip device (Abbott Vascular, Abbott Park, Illinois) and compare the results with surgery in this population. BACKGROUND:The EVEREST II (Endovascular Valve...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1016/j.jacc.2011.12.023
更新日期:2012-04-03 00:00:00
abstract:OBJECTIVES:The aim of this study was to determine the impact of the metabolic syndrome (MS) on operative mortality after a coronary artery bypass grafting surgery (CABG). BACKGROUND:Diabetes and obesity are highly prevalent among patients undergoing CABG. However, it remains unclear whether these factors have a signif...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2007.04.075
更新日期:2007-08-28 00:00:00
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journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章
doi:10.1016/j.jacc.2010.05.007
更新日期:2010-09-07 00:00:00
abstract:OBJECTIVES:The purpose of this study was to evaluate the role of the myocardial redox state in the development of in-hospital complications after cardiac surgery and the effect of statins on the myocardial redox state. BACKGROUND:Statins improve clinical outcome after cardiac surgery, but it is unclear whether they ex...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jacc.2011.08.062
更新日期:2012-01-03 00:00:00
abstract:OBJECTIVES:The aim of this study was to determine the effects of physical activity on systemic blood pressure (BP) and early markers of atherosclerosis in pre-pubertal obese children. BACKGROUND:Hypertension and endothelial dysfunction are premature complications of obesity. METHODS:We performed a 3-month randomized ...
journal_title:Journal of the American College of Cardiology
pub_type: 杂志文章,随机对照试验
doi:10.1016/j.jacc.2009.08.030
更新日期:2009-12-15 00:00:00
abstract::There is increased interest in and use of cardiac computed tomographic and magnetic resonance imaging as the technology continues to improve. We have many small single-center trials on the diagnostic accuracy of these techniques, but no studies that show a patient benefit from testing. The American College of Cardiolo...
journal_title:Journal of the American College of Cardiology
pub_type: 评论,杂志文章
doi:10.1016/j.jacc.2006.09.056
更新日期:2007-05-08 00:00:00