Abstract:
:Increased activity of matrix metalloproteinases (MMPs) has been implicated in numerous disease processes, including tumor growth and metastasis, arthritis, and periodontal disease. It is now becoming increasingly clear that extracellular matrix degradation by MMPs is also involved in the pathogenesis of cardiovascular disease, including atherosclerosis, restenosis, dilated cardiomyopathy, and myocardial infarction. Administration of synthetic MMP inhibitors in experimental animal models of these cardiovascular diseases significantly inhibits the progression of, respectively, atherosclerotic lesion formation, neointima formation, left ventricular remodeling, pump dysfunction, and infarct healing. This review focuses on the role of MMPs in cardiovascular disease, in particular myocardial infarction and the subsequent progression to heart failure. MMPs, which are present in the myocardium and capable of degrading all the matrix components of the heart, are the driving force behind myocardial matrix remodeling. The recent finding that acute pharmacological inhibition of MMPs or deficiency in MMP-9 attenuates left ventricular dilatation in the infarcted mouse heart led to the proposal that MMP inhibitors could be used as a potential therapy for patients at risk for the development of heart failure after myocardial infarction. Although these promising results encourage the design of clinical trials with MMP inhibitors, there are still several unresolved issues. This review describes the biology of MMPs and discusses new insights into the role of MMPs in several cardiovascular diseases. Attention will be paid to the central role of the plasminogen system as an important activator of MMPs in the remodeling process after myocardial infarction. Finally, we speculate on the use of MMP inhibitors as potential therapy for heart failure.
journal_name
Circ Resjournal_title
Circulation researchauthors
Creemers EE,Cleutjens JP,Smits JF,Daemen MJdoi
10.1161/hh1501.094396subject
Has Abstractpub_date
2001-08-03 00:00:00pages
201-10issue
3eissn
0009-7330issn
1524-4571journal_volume
89pub_type
杂志文章,评审abstract::We tested the hypothesis that activation of transient receptor potential vanilloid type-1 (TRPV1) by capsaicin prevents adipogenesis. TRPV1 channels in 3T3-L1-preadipocytes and visceral adipose tissue from mice and humans were detected by immunoblotting and quantitative real-time RT-PCR. The effect of TRPV1 on cytosol...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000262653.84850.8b
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abstract::The daily rate of cell replication in the aortic endothelium of the normal rat falls from a maximum of 13% at birth to 0.1-0.3% at age 5-6 months. This residual rate of replication largely represents the turnover rate of the endothelium in normal animals. After renal hypertension of 2-3 weeks duration, however, the ra...
journal_title:Circulation research
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doi:10.1161/01.res.41.2.248
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abstract::The aim of this study is to quantify the porcine coronary arterial branching pattern and to use this quantification for the interpretation of flow heterogeneity. Two casts of the coronary arterial tree were made at diastolic arrest and maximal dilation. The relation between length and diameter of arterial segments was...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.5.1200
更新日期:1992-11-01 00:00:00
abstract::The role of the central nervous system in the mechanism(s) involved in acute carotid baroreflex resetting was studied in six conscious, chronically instrumented, aortic-denervated dogs. Dogs were prepared for reversible vascular isolation of the carotid sinuses. Acute baroreflex resetting was induced by holding the le...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.65.1.63
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.83.11.1165
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abstract:RATIONALE:Congenital heart disease (CHD) is among the most common birth defects. Most cases are of unknown pathogenesis. OBJECTIVE:To determine the contribution of de novo copy number variants (CNVs) in the pathogenesis of sporadic CHD. METHODS AND RESULTS:We studied 538 CHD trios using genome-wide dense single nucle...
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pub_type: 临床试验,杂志文章
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.55.1.120
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.66.3.662
更新日期:1990-03-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/hh1101.091190
更新日期:2001-06-08 00:00:00
abstract::The changes in renal function produced by endogenous synthesis of prostaglandins by the kidney were evaluated by infusing sodium arachidonate, the prescursor of the prostaglandins, into one renal artery of the dog. These changes were compared with those produced by similar infusions on performed prostaglandin (PG) E2 ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.36.1.197
更新日期:1975-01-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.306993
更新日期:2015-08-28 00:00:00
abstract:RATIONALE:Nav1.5 (SCN5A) is the primary cardiac voltage-gated Nav channel. Nav1.5 is critical for cardiac excitability and conduction, and human SCN5A mutations cause sinus node dysfunction, atrial fibrillation, conductional abnormalities, and ventricular arrhythmias. Further, defects in Nav1.5 regulation are linked wi...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.305154
更新日期:2014-11-07 00:00:00
abstract::Herein, we show that the paired-related homeobox gene, Prx1, is required for lung vascularization. Initial studies revealed that Prx1 localizes to differentiating endothelial cells (ECs) within the fetal lung mesenchyme, and later within ECs forming vascular networks. To begin to determine whether Prx1 promotes EC dif...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000130656.72424.20
更新日期:2004-06-11 00:00:00
abstract::Despite intense interest in understanding the differentiation of vascular smooth muscle, very little is known about the cellular and molecular mechanisms that control differentiation of this cell type. Progress in this field has been hampered by the lack of an inducible in vitro system for study of the early steps of ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.76.5.742
更新日期:1995-05-01 00:00:00
abstract::During cardiac development, the epicardium is the source of multipotent mesenchymal cells, which give rise to endothelial and smooth muscle cells in coronary vessels and also, possibly, to cardiomyocytes. The aim of the present study was to determine whether stem cells are retained in the adult human and murine epicar...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.107.150755
更新日期:2007-12-07 00:00:00
abstract::The relations between atrial natriuretic peptide (ANP) binding sites in the renal medulla, plasma ANP concentration, and ventricular dysfunction have been studied in rats 4 weeks after myocardial infarction induced by left coronary artery ligation. Plasma ANP concentration was measured by radioimmunoassay, and quantit...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.62.1.155
更新日期:1988-01-01 00:00:00
abstract:RATIONALE:Although the health effects of beta carotene have been studied extensively, a systematic examination of serum concentrations and long-term mortality, including cardiovascular disease mortality, has not been reported. OBJECTIVE:Explore whether serum beta carotene is associated with overall and cause-specific ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.118.313409
更新日期:2018-12-07 00:00:00
abstract::Shear stress caused by the frictional forces of a fluid moving over a cell monolayer is an important regulator of gene expression. In this study, we investigated the effect of shear stress on angiotensin-converting enzyme (ACE) expression and promoter activity in vitro and on local vascular ACE activity in vivo. ACE a...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.80.3.312
更新日期:1997-03-01 00:00:00
abstract::High sodium intake (HNa) increases brain ouabainlike activity (OLA) in rats. In spontaneously hypertensive rats (SHR), HNa exaggerates development of hypertension and pressor and sympathoexcitatory responses to stress. To investigate whether dietary sodium-induced changes in brain OLA play a functional role, responses...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.70.2.430
更新日期:1992-02-01 00:00:00
abstract:RATIONALE:The low-density lipoprotein (LDL) receptor (LDLR) is a central determinant of circulating LDL-cholesterol and as such subject to tight regulation. Recent studies and genetic evidence implicate the inducible degrader of the LDLR (IDOL) as a regulator of LDLR abundance and of circulating levels of LDL-cholester...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.115.307298
更新日期:2016-02-05 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.50.4.527
更新日期:1982-04-01 00:00:00
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pub_type: 杂志文章
doi:10.1161/CIRCRESAHA.109.193870
更新日期:2009-08-28 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章
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更新日期:1999-06-11 00:00:00
abstract::The cardiac troponin T (TnT) I79N mutation has been linked to familial hypertrophic cardiomyopathy and high incidence of sudden death, despite causing little or no cardiac hypertrophy in patients. Transgenic mice expressing mutant human TnT (I79N-Tg) have increased cardiac contractility, but no ventricular hypertrophy...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.RES.0000059562.91384.1A
更新日期:2003-03-07 00:00:00
abstract::Recent evidence suggests that functional diversity of vascular smooth muscle is produced in part by a differential expression of ion channels. The aim of the present study was to examine the role of Ca(2+)-activated K(+) channels (K(Ca) channels) in the expression of smooth muscle cell functional phenotype. We found t...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.85.9.e33
更新日期:1999-10-29 00:00:00
abstract::The purpose of these experiments was to determine whether or not acetylcholine modulated the electrophysiological effects of isoproterenol on canine cardiac Purkinje fibers. Conventional microelectrode techniques were used. Predictably, isoproterenol produced shortening of action potential duration; acetylcholine sign...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.44.3.378
更新日期:1979-03-01 00:00:00
abstract::Rho regulates various cell functions, including cell morphology and motility. However, the functional role of Rho on the signaling pathway in myocardial cells (MCs) is unknown. In the present study, we attempted to explore the mode of Rho action for c-fos gene expression in MCs. Expression of the c-fos promoter/enhanc...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.81.5.672
更新日期:1997-11-01 00:00:00
abstract::A method was developed for recording isometric tension from isolated small arteries (mean internal diameter, 169 microns) and veins (mean internal diameter, 273 microns) of the term fetal lung and was then applied to the study of the mechanisms controlling perinatal pulmonary hemodynamics. The specific purpose was to ...
journal_title:Circulation research
pub_type: 杂志文章
doi:10.1161/01.res.71.2.320
更新日期:1992-08-01 00:00:00
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journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2009-09-11 00:00:00
abstract::Troponin is essential for the regulation of cardiac contraction. Troponin is a sarcomeric molecular switch, directly regulating the contractile event in concert with intracellular calcium signals. Troponin isoform switching, missense mutations, proteolytic cleavage, and posttranslational modifications are known to dir...
journal_title:Circulation research
pub_type: 杂志文章,评审
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更新日期:2004-02-06 00:00:00