基质金属蛋白酶/基质金属蛋白酶组织抑制剂与心房颤动

基质金属蛋白酶是一个细胞外基质降解酶家族,基质金属蛋白酶组织抑制剂是其内源性抑制物.二者平衡在细胞外基质合成及降解过程中起重要作用,与心房颤动过程中心房结构重塑,即心房纤维化及心房扩大相关.目前研究显示基质金属蛋白酶/基质金属蛋白酶组织抑制剂失衡与心房颤动的发生、发展及复发相关,抑制基质金属蛋白酶可改善心房重塑并阻止心房颤动进展.恢复基质金属蛋白酶/基质金属蛋白酶组织抑制剂平衡可能成为治疗心房颤动的新型治疗途径.     

基质金属蛋白酶及其抑制剂在心肌疾病中的研究进展

心肌疾病常伴随着心肌细胞外基质成分的改变,细胞外基质合成或降解失衡是心肌疾病发病过程中重要的环节。细胞外基质的合成与降解主要与位于其间的基质金属蛋白酶及其特异性组织抑制剂的活性有关。基质金属蛋白酶可以分解细胞外基质,从而改变组织的形态结构。基质金属蛋白酶与特异性组织抑制剂之间的动态平衡与心肌疾病发病过程中心肌重构和心衰进展有重要关系。     

组织蛋白酶与心血管疾病的研究进展

学者们认为隶属于半胱氨酸蛋白酶（cysteine protease）的组织蛋白酶（cathepsins）主要作用是在溶酶体酸性条件下,降解不必要的细胞器及蛋白质,使其再被利用.然而最近研究显示,组织蛋白酶家族成员和其他细胞外蛋白酶（如基质金属蛋白酶和丝氨酸蛋白酶）一样,对细胞外基质的重塑、间质基质的降解以及细胞信号传递和细胞凋亡起重要作用.本综述重点叙述组织蛋白酶生物学特征（结构、合成、加工、激活、分泌、活性调控和功能）,以及参与各种心血管疾病的发病机制,尤其是关于循环血中组织蛋白酶水平作为诊断心血管疾病、预后判定和药物靶目标的应用潜能.     

基质金属蛋白酶与慢性阻塞性肺疾病

基质金属蛋白酶 (MMPs)是一组具有相同功能、结构高度同源、依赖锌离子的内肽酶的总称 ,其主要作用是降解细胞外基质 (ECM)和基底膜。适时的细胞外基质破坏是胚胎生长、繁殖、形态发生、组织再吸收和重建所必需的。因而 ,MMPs在胚胎发生、排卵、器官形成、组织塑型和伤口愈合等生理过程中起重要作用 ,但其过多表达和激活则与类风湿性关节炎、心血管疾病、肿瘤生长及转移等病理过程有密切的关系。研究发现 ,ECM降解是肺气肿形成的重要环节 ,因此 ,MMPs在慢性阻塞性肺疾病 (COPD)的发生发展中亦起重要作用。而且 ,MMPs抑制剂能抑制 …     

基质金属蛋白酶及其组织抑制剂在胸腔积液诊断中的评价

胸腔积液是最常见的胸膜疾病,病因复杂,诊断困难.近年来,与细胞外基质降解和沉淀有关的基质金属蛋白酶及其组织抑制剂在胸腔积液发生发展过程中的作用得到了更为深入的研究,这也为胸腔积液的诊断和鉴别诊断提供了新的思路.本文对基质金属蛋白酶及其组织抑制剂与各种原因所致胸腔积液的关系作一综述.     

基质金属蛋白酶及组织金属蛋白酶抑制剂与类风湿性关节炎

基质金属蛋白酶(MMPs)是降解细胞外基质(ECM)的一种重要的蛋白酶,对类风湿性关节炎的发生、发展有重要作用.组织金属蛋白酶抑制剂(TIMPs)是MMPs的天然抑制物,MMPs/TIMPs两者比例可作为反映疾病活动程度及预后的重要指标.     

基质金属蛋白酶与急性肺损伤/急性呼吸窘迫综合征

基质金属蛋白酶,在体内可由多种基质细胞和炎症细胞产生,能降解基底膜和细胞外基质的多种蛋白成分,各种致病因子的刺激可引起其异常表达,在组织重构与修复、炎症反应、肿瘤侵袭和转移中发挥重要作用。     

基质金属蛋白酶与血管损伤后再狭窄的研究现状

基质金属蛋白酶（MMPs）是一组能特异地降解细胞外基质成分的依赖锌酶家族,在组织重构中起重要作用,尤其在血管损伤后重建等诸多领域有着重要意义。MMPs能够催化降解血管平滑肌细胞周围基底膜,促进平滑肌细胞转化迁移,形成新生内膜,造成血管损伤后再狭窄。了解其作用机制有助于预防和治疗相关疾病。     

基质金属蛋白酶与呼吸系统疾病

基质金属蛋白酶,在体内可由多种基质细胞和炎症细胞产生,能降解细胞外基质中的多种蛋白成份,各种致病因子的刺激可引起其异常表达,在慢性阻塞性肺病(COPD)、肺间质纤维化、支气管哮喘、肺癌等呼吸系统疾病的组织重建与修复、炎症反应、肿瘤侵袭和转移中发挥重要作用。     

基质金属蛋白酶与呼吸系统疾病

基质金属蛋白酶，在体内可由多种基质细胞和炎症细胞产生，能降解细胞外基质中的多种蛋白成分，各种致病因子的刺激可引起其异常表达，在慢性阻塞性肺病（COPD）、肺间质纤维化、支气管哮喘、肺癌等呼吸系统疾病的组织重建与修复、炎症反应、肿瘤侵袭和转移中发挥重要作用。     

心肌细胞外基质重塑与充血性心力衰竭

心肌细胞外基质的主要功能是使心肌细胞正常排列、支持组织结构。但是近几年的研究发现认为,细胞外基质在影响细胞行为中扮演着各种各样的复杂的角色,例如,细胞外基质在细胞移植、细胞增殖、细胞的结构支持和细胞之间的信号转导中都起着很重要的作用。因此认为,心肌细胞外基质不仅仅是一个静态的组织结构,它是一个由基质分子,信号蛋白,结构蛋白和跨膜蛋白所组成的动态变化的联合系统。心肌细胞外基质重塑将会导致心肌重塑从而导致心力衰竭。     

阿托伐他汀对心肌肥厚大鼠细胞外基质重塑的抑制作用

目的探讨阿托伐他汀对去甲肾上腺素诱导的心肌肥厚大鼠细胞外基质重塑的影响及其可能的机制.方法雄性SD大鼠随机分为三组(1)对照组,(2)去甲肾上腺素组[1.06 mg/(kg·d)×15 d],(3) 去甲肾上腺素+阿托伐他汀组[50 mg/(kg·d)×15 d].去甲肾上腺素ip,2次/d,15 d,建立心肌肥厚模型.应用超声心动图及病理学方法评价整体心肌肥厚及组织胶原表达.用逆转录-聚合酶链反应法(RT-PCR)及免疫组化检测细胞外基质调节因子-基质金属蛋白酶(MMP-9)及其生理性抑制剂(TIMP-1)和转化生长因子β1(TGF-β1)mRNA和蛋白表达.结果去甲肾上腺素组大鼠发生左心室肥厚及纤维化,胶原含量及MMP-9、TIMP-1和TGF-β-1蛋白、mRNA表达显著高于健康对照组(P<0.01).阿托伐他汀能减少心肌中总体胶原及Ⅰ、Ⅲ型胶原的合成及MMP-9、TGF-β-1表达(P<0.01).结论 MMP-9、TIMP-1和TGF-β-1与心肌肥厚大鼠的细胞外基质重塑有关.阿托伐他汀能有效防治心肌纤维化及细胞外基质重塑,这一效应与其降低心肌中高表达的MMP-9和TGF-β-1有关.     

Ventricular remodeling and function: Insights using murine echocardiography

Extracellular matrix disturbances play an important role in the development of ventricular remodeling and failure. Genetically modified mice with abnormalities in the synthesis and degradation of extracellular matrix have been generated, in particular mice with deletion or overexpression of matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs). Echocardiography is ideally suited to serially evaluate left ventricular (LV) size and function, thus defining the progression of LV remodeling and failure. This Review describes the echocardiographic parameters that may provide insights into the development of ventricular remodeling and heart failure. The application of echocardiography to study LV remodeling and function after myocardial infarction and LV pressure-overload in wild-type mice and mice deficient or overexpressing MMPs or TIMPs is then detailed. Finally, using the example of mice deficient in nitric oxide synthase 3, a cautionary example is given illustrating discrepancies between the cardiac echocardiographic phenotype and modifications of the extracellular matrix.     

Matrix modulation and heart failure: new concepts question old beliefs

PURPOSE OF REVIEW: Myocardial remodeling is a complex process involving several molecular and cellular factors. Extracellular matrix has been implicated in the remodeling process. Historically, the myocardial extracellular matrix was thought to serve solely as a means to align cells and provide structure to the tissue. Although this is one of its important functions, evidence suggests that the extracellular matrix plays a complex and divergent role in influencing cell behavior. This paper characterizes some of the notable studies on this dynamic entity and on adverse myocardial remodeling that have been published over the past year, which further question the belief that the extracellular matrix is a static structure. RECENT FINDINGS: Progress has been made in understanding how the extracellular matrix is operative in the three major conditions (myocardial infarction, left ventricular hypertrophy due to overload, and dilated cardiomyopathy) that involve myocardial remodeling. Several studies have examined plasma profiles of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases following myocardial infarction and during left ventricular hypertrophy as surrogate markers of remodeling/remodeled myocardium. It has been demonstrated that bioactive signaling molecules and growth factors, proteases, and structural proteins influence cell-matrix interactions in the context of left ventricular hypertrophy. Finally, studies that either removed or added tissue inhibitor of metalloproteinases species in the myocardium demonstrated the importance of this regulatory protein in the remodeling process. SUMMARY: Understanding the cellular and molecular triggers that in turn give rise to changes in the extracellular matrix could provide opportunities to modify the remodeling process.     

Myocardial myocyte remodeling and fibrosis in the cardiometabolic syndrome

Myocardial cellular and extracellular matrix remodeling are important in the development of left ventricular hypertrophy and are essential for the adaptive and maladaptive changes associated with the cardiometabolic syndrome. This brief review of myocyte remodeling also presents preliminary observational findings regarding myocardial adaptive hypertrophy remodeling, including an increase in mitochondria and capillaries, convolutions and lengthening of intercalated discs, the addition of sarcomeres, thickened Z lines, and the novel presence of pericapillary fibrosis (in addition to perivascular arteriolar fibrosis). The 11-week-old TG(mREN-2)27 transgene rat model of tissue angiotensin II overexpression, which develops hypertension and insulin resistance, was chosen to examine both myocyte hypertrophy and extracellular matrix fibrosis. This review and the preliminary observational findings may provide the clinician and researcher a better understanding of remodeling changes in the myocardium and ultimately foster earlier recognition and therapeutic interventions.     

基质金属蛋白酶与动脉粥样硬化

基质金属蛋白酶 (MMP)降解细胞外基质 (ECM ) ,参与动脉粥样硬化 (AS)的细胞外基质重构过程 ,与AS的形成、斑块破裂及再狭窄密切相关。适度调节金属蛋白酶的活性为防治AS提供了新的靶点。     

Transforming growth factor beta inhibition increases mortality and left ventricular dilatation after myocardial infarction

BACKGROUND: Transforming growth factor (TGF)-beta is a locally generated cytokine involved in healing processes and tissue fibrosis, all relevant for cardiac remodeling and the development of heart failure after myocardial infarction (MI). However, data regarding the function of TGF-beta after ischemic injury are inconclusive. METHODS AND RESULTS: We tested the effect of TGF-beta inhibition by application of a blocking antibody in mice with MI. Starting 1 week before or 5 days after coronary artery ligation mice were treated with intraperitoneal injections of an anti-TGF-beta (5 mg/kg bodyweight 1D11, Genzyme) or control antibody. Mortality over 8 weeks was significantly higher in the groups treated with the anti-TGF-beta antibody. Both, pre or post MI treatments were associated with increased left ventricular dilatation after MI as determined by serial echocardiography. In anti-TGF-beta treated mice collagen production decreased and matrix-metalloproteinase expression increased. However, the expression of TGF pro-inflammatory cytokine TNF-alpha was not altered by the treatment. Anti-TGF-beta treatment before or after coronary artery ligation increases mortality and worsens left ventricular remodeling in mice with non-reperfused MI. The detrimental effects of TGF-beta inhibition may be mediated by alterations in extracellular matrix remodeling.     

基质金属蛋白酶及其抑制剂与心肌梗死后心室重塑

基质金属蛋白酶是心肌梗死后降解细胞外胶原基质的驱动力量 ,可导致心室扩张和心力衰竭的发生。内源性及外源性基质金属蛋白酶抑制剂在一定程度上能抑制其降解作用 ,减缓心室重塑的进程。本综述详细阐述了基质金属蛋白酶及其抑制剂与心肌梗死后心室重塑之间的关系 ,并探讨了基质金属蛋白酶抑制剂在应用的剂型、时点上存在的一些争议性问题。     

基质金属蛋白酶家族及其在心力衰竭心室重构中的作用

在心力衰竭的发展过程中常发生心室重构 ,包括心肌细胞的肥厚和细胞外基质的变化 ,后者是心室重构的重要原因。基质金属蛋白酶是一组能特异地降解细胞外基质成分的 Zn2 + 依赖的酶家族 ,在左心室的重构过程中起重要作用。