Abstract:
BACKGROUND:Several recent studies attempted to classify plaques as those prone to cause clinical manifestations (vulnerable, atheromatous plaques) or those less frequently associated with acute thrombotic complication (stable, fibrous plaques). Defining the cellular and molecular mechanisms that underlie these morphological features remains a challenge. Because interstitial forms of collagen determine the biomechanical strength of the atherosclerotic lesion, this study investigated expression of the collagen-degrading matrix metalloproteinase (MMP) interstitial collagenase-3 (MMP-13) and the previously studied MMP-1 in human atheroma and used a novel technique to test the hypothesis that collagenolysis in atheromatous lesions exceeds that in fibrous human atherosclerotic lesions. METHODS AND RESULTS:Human carotid atherosclerotic plaques, similar in size, were separated by conventional morphological characteristics into fibrous (n=10) and atheromatous (n=10) lesions. Immunohistochemical and Western blot analysis demonstrated increased levels of MMP-1 and MMP-13 in atheromatous versus fibrous plaques. In addition, collagenase-cleaved type I collagen, demonstrated by a novel cleavage-specific antibody, colocalized with MMP-1- and MMP-13-positive macrophages. Macrophages, rather than endothelial or smooth muscle cells, expressed MMP-13 and MMP-1 on stimulation in vitro. Furthermore, Western blot analysis demonstrated loss of interstitial collagen type I and increased collagenolysis in atheromatous versus fibrous lesions. Finally, atheromatous plaques contained higher levels of proinflammatory cytokines, activators of MMPs. CONCLUSIONS:This report demonstrates that atheromatous rather than fibrous plaques might be prone to rupture due to increased collagenolysis associated with macrophages, probably mediated by the interstitial collagenases MMP-1 and MMP-13.
journal_name
Circulationjournal_title
Circulationauthors
Sukhova GK,Schönbeck U,Rabkin E,Schoen FJ,Poole AR,Billinghurst RC,Libby Pdoi
10.1161/01.cir.99.19.2503subject
Has Abstractpub_date
1999-05-18 00:00:00pages
2503-9issue
19eissn
0009-7322issn
1524-4539journal_volume
99pub_type
杂志文章相关文献
CIRCULATION文献大全abstract::Acute intravenous administration of the new beta 1-adrenergic receptor partial agonist xamoterol lowers left ventricular end-diastolic pressure and improves the isovolumic indexes of inotropic state and relaxation. To determine if these hemodynamic changes were maintained after prolonged administration, the dose-respo...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract:BACKGROUND:Pharmacological evidence has implicated ATP-sensitive K(+) (K(ATP)) channels as the effectors of cardioprotection, but the relative roles of mitochondrial (mitoK(ATP)) and sarcolemmal (surfaceK(ATP)) channels remain controversial. METHODS AND RESULTS:We examined the effects of the K(ATP) channel blocker HMR...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.101.20.2418
更新日期:2000-05-23 00:00:00
abstract:BACKGROUND:Children stable at home with dilated cardiomyopathy remain at risk of death; there is evidence of survival benefit for transplantation out to 4 years postoperatively. The limited supply of donor organs makes risk stratification imperative, but although cardiopulmonary exercise test is well established as a p...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.111.035956
更新日期:2011-10-18 00:00:00
abstract::We determined the efficacy, pharmacokinetics, and plasma concentration-response relationships of propafenone, a promising new antiarrhythmic drug. Thirteen patients with frequent and complex ventricular premature beats were studied after receiving four increasing doses, during drug washout and during a randomized doub...
journal_title:Circulation
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1161/01.cir.68.3.589
更新日期:1983-09-01 00:00:00
abstract::Cardiovascular disease is the number one cause of death for women in the United States. Of the 1.3 million active duty service members, 16.3% are currently women, and the number of women veterans is expected to increase. Women veterans have higher rates of cardiovascular disease than civilian women and present a uniqu...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.118.037748
更新日期:2019-02-19 00:00:00
abstract::Between 1972 and 1984, 100 consecutive neonates (less than or equal to 30 days old) underwent repair of coarctation of the aorta. Mean (+/- SD) age at operation was 12.0 +/- 8.0 days; mean weight was 3.1 +/- 0.5 kg. Simple coarctation was present in 29 patients (group I), 32 patients had additional ventricular septal ...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1986-09-01 00:00:00
abstract:BACKGROUND:Timely primary percutaneous coronary intervention (PPCI) cannot be offered to all patients with ST-segment-elevation myocardial infarction (STEMI). Pharmaco-invasive (PhI) strategy has been proposed as a valuable alternative for eligible patients with STEMI. We conducted a randomized study to compare the eff...
journal_title:Circulation
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1161/CIRCULATIONAHA.117.030582
更新日期:2017-10-17 00:00:00
abstract:BACKGROUND:Elevated pulse pressure is associated strongly with adverse cardiovascular outcome; however, the genetic basis of this condition is unknown. This study examined whether genotypic variation in the extracellular matrix protein fibrillin-1, the Marfan gene, was associated with aortic stiffening and therefore co...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/hc0702.104129
更新日期:2002-02-19 00:00:00
abstract:BACKGROUND:There is no treatment proven to limit the growth of abdominal aortic aneurysms, in which the histological hallmarks include inflammation and medial atrophy, with apoptosis of smooth muscle cells and destruction of elastin. METHODS AND RESULTS:Aneurysm biopsies were used for explant cultures, the preparation...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.100.1.48
更新日期:1999-07-06 00:00:00
abstract:BACKGROUND:The role of a cluster of risk factors characteristic for the insulin resistance syndrome as a predictor for coronary heart disease (CHD) has not been studied previously. METHODS AND RESULTS:Clustering of cardiovascular risk factors was analyzed by factor analysis to investigate whether these clusters (facto...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.100.2.123
更新日期:1999-07-13 00:00:00
abstract:BACKGROUND:MicroRNAs (miRs) participate in many cardiac pathophysiological processes, including ischemia/reperfusion (I/R)-induced cardiac injury. Recently, we and others observed that miR-494 was downregulated in murine I/R-injured and human infarcted hearts. However, the functional consequence of miR-494 in response ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.110.964684
更新日期:2010-09-28 00:00:00
abstract::Twenty-two patients who underwent anatomic correction of transposition of the great arteries at the arterial level at the age of 8 weeks to 14 years were reinvestigated 1-4.6 years (mean 2.0 years) after operation. A Dacron tube was used to bridge the gap between the proximal pulmonary route and the distal pulmonary a...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1982-08-01 00:00:00
abstract:BACKGROUND:Atherosclerosis is a systemic disease that underlies clinical cardiovascular disease. The radiographic finding of abdominal aortic calcific deposits is an indicator of the presence of aortic atherosclerosis and an independent predictor of cardiovascular disease events. Little is known about the heritability ...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.0000022663.26468.5b
更新日期:2002-07-16 00:00:00
abstract:BACKGROUND:To evaluate the effect of plasminogen activator inhibitor type 1 (PAI-1) levels on the clearance of total tissue plasminogen activator (TPA) antigen, we studied the clearance of active TPA and TPA/PAI-1 complex in subjects with low (181+/-109 pmol/L; n=7) and high (1166+/-322 pmol/L; n=4) baseline active PAI...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.96.3.761
更新日期:1997-08-05 00:00:00
abstract:BACKGROUND:Endothelial dysfunction may contribute to the risk of premature atherosclerosis in patients with diabetes. Endothelin (ET-1) may be involved in this process by activating smooth muscle cell mitogenesis and leukocyte adhesion. We sought to assess the activity of endogenous ET-1 in a group of patients with typ...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/01.cir.0000032260.01569.64
更新日期:2002-10-01 00:00:00
abstract:BACKGROUND:Secretoneurin is a neuropeptide located in nerve fibers along blood vessels, is upregulated by hypoxia, and induces angiogenesis. We tested the hypothesis that secretoneurin gene therapy exerts beneficial effects in a rat model of myocardial infarction and evaluated the mechanism of action on coronary endoth...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.111.076950
更新日期:2012-11-20 00:00:00
abstract:BACKGROUND:Cardiomyocyte grafting augments myocyte numbers in the heart. We investigated (1) how developmental stage influences graft survival; (2) whether acutely necrotic or healing cardiac lesions support grafts; and (3) the differentiation and integration of cardiomyocyte grafts in injured hearts. METHODS AND RESU...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.100.2.193
更新日期:1999-07-13 00:00:00
abstract:BACKGROUND:Lipoprotein oxidation plays an important part in atherogenesis. Autoantibodies to oxidation-specific epitopes of LDL occur in plasma and atherosclerotic lesions of humans and animals. The potential role of these autoantibodies in atherogenesis still remains unsolved. We studied the relationship between diffe...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.CIR.0000092891.55157.A7
更新日期:2003-10-28 00:00:00
abstract:BACKGROUND:In a correlative functional/histopathologic study, we investigated the regional deformation characteristics of both chronic nontransmural and transmural infarctions before and after a dobutamine challenge. METHODS AND RESULTS:After stenosing copper-coated stent implantation to produce circumflex artery endo...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.0000050146.66577.4b
更新日期:2003-02-18 00:00:00
abstract:BACKGROUND:The atrioventricular node (AVN) is the only normal electrical link between the upper and lower chambers of the heart. The AVN modulates transmission of impulses, thus coordinating the contraction of the atria and ventricles. METHODS AND RESULTS:Structural and functional complexity, combined with the absence...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.98.1.54
更新日期:1998-07-07 00:00:00
abstract::The pericardium, because of the nature of its pressure-volume relation, can influence left ventricular diastolic and systolic pump function. During an acute increase in heart size that results in the stretching of the pericardium, the elastic properties of the pericardium restrict further cardiac dilatation and curtai...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract:BACKGROUND:Recognition of rates and causes of hard, patient-centered outcomes of death and cerebrovascular events (CVEs) after heart rhythm disorder management (HRDM) procedures is an essential step for the development of quality improvement programs in electrophysiology laboratories. Our primary aim was to assess and ...
journal_title:Circulation
pub_type: 杂志文章,多中心研究
doi:10.1161/CIRCULATIONAHA.117.030523
更新日期:2018-01-02 00:00:00
abstract:BACKGROUND:There are few studies of cardiac autonomic nervous activity (CANA) in patients with congenital heart disease. Methods and Results-We evaluated CANA in 54 patients after closure of an atrial/ventricular septal defect (group A), 54 patients after successful right ventricular outflow tract reconstruction (RVOTR...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/01.cir.102.22.2732
更新日期:2000-11-28 00:00:00
abstract::The goals of electrocardiographic (ECG) monitoring in hospital settings have expanded from simple heart rate and basic rhythm determination to the diagnosis of complex arrhythmias, myocardial ischemia, and prolonged QT interval. Whereas computerized arrhythmia analysis is automatic in cardiac monitoring systems, compu...
journal_title:Circulation
pub_type: 指南,杂志文章,实务指引
doi:10.1161/01.CIR.0000145144.56673.59
更新日期:2004-10-26 00:00:00
abstract:BACKGROUND:Estradiol (E2) modulates the kinetics of circulating endothelial progenitor cells (EPCs) and favorably affects neovascularization after ischemic injury. However, the roles of estrogen receptors alpha (ER alpha) and beta (ER beta) in EPC biology are largely unknown. METHODS AND RESULTS:In response to E2, mig...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.106.631465
更新日期:2006-11-21 00:00:00
abstract:BACKGROUND:Serotonin (5-hydroxytryptamine; 5-HT) overproduction is responsible for cardiac valvular disease in patients with carcinoid tumors. Reduced 5-HT inactivation is one proposed mechanism of the valvulopathy observed in individuals treated with the appetite suppressants fenfluramine and phentermine. One key prot...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.105.554667
更新日期:2006-01-03 00:00:00
abstract:BACKGROUND:Despite successful surgical correction, morbidity of patients with coarctation of the aorta is increased. It is well known that these patients have impaired elastic properties of the prestenotic arteries. To find out whether these abnormalities are primarily present or develop later, we studied 17 newborns b...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.104.529792
更新日期:2005-06-21 00:00:00
abstract:BACKGROUND:The incidence of syncope exhibits a daily pattern with more occurrences in the morning, possibly as a result of influences from the endogenous circadian system and/or the daily pattern of behavioral/emotional stimuli. This study tested the hypothesis that the circadian system modulates cardiovascular respons...
journal_title:Circulation
pub_type: 杂志文章
doi:10.1161/CIRCULATIONAHA.110.943019
更新日期:2011-03-08 00:00:00
abstract:BACKGROUND:Myocardial perfusion during adenosine-induced hyperemia is used both in clinical diagnosis of coronary heart disease and for scientific investigations of the myocardial microcirculation. The objective of this study was to clarify whether adenosine-induced hyperemia is dependent on endothelial NO production o...
journal_title:Circulation
pub_type: 临床试验,杂志文章
doi:10.1161/hc4401.098293
更新日期:2001-11-06 00:00:00
abstract::The indications for biventricular versus left ventricular mechanical circulatory support as a bridge to cardiac transplantation are not well established. In this study, 27 potential heart transplant candidates who were in imminent risk of dying before donor heart procurement were implanted with Thoratec prosthetic ven...
journal_title:Circulation
pub_type: 杂志文章
doi:
更新日期:1989-11-01 00:00:00