Contribution of extracellular matrix to the mechanical properties of the heart

Extracellular matrix (ECM) components play essential roles in development, remodeling, and signaling in the cardiovascular system. They are also important in determining the mechanics of blood vessels, valves, pericardium, and myocardium. The goal of this brief review is to summarize available information regarding the mechanical contributions of ECM in the myocardium. Fibrillar collagen, elastin, and proteoglycans all play crucial mechanical roles in many tissues in the body generally and in the cardiovascular system specifically. The myocardium contains all three components, but their mechanical contributions are relatively poorly understood. Most studies of ECM contributions to myocardial mechanics have focused on collagen, but quantitative prediction of mechanical properties of the myocardium, or changes in those properties with disease, from measured tissue structure is not yet possible. Circumstantial evidence suggests that the mechanics of cardiac elastin and proteoglycans merit further study. Work in other tissues used a combination of correlation, modification or digestion, and mathematical modeling to establish mechanical roles for specific ECM components; this work can provide guidance for new experiments and modeling studies in myocardium.     

The role of proteoglycans in pulmonaryedema development

Pulmonary gas exchange critically depends upon the hydration state and the thinness of the interstitial tissue layer within the alveolo-capillary membrane. In the interstitium, fluid freely moving within the fibrous extracellular matrix (ECM) equilibrates with water chemically bound to hyaluronic acid and proteoglycans (PGs). The dynamic equilibrium between these two phases is set and maintained by the transendothelial fluid and solutes exchanges, by the convective outflows into the lymphatic system, and by the mechanical and hydrophilic properties of the solid elements of the ECM. The fibrous ECM components, in particular the chondroitin sulfate proteoglycan (CS-PG) and the heparan-sulfate proteoglycan (HS-PG) families, play a major role in the maintenance of tissue fluid homeostasis. In fact, they provide: (a) a perivascular and interstitial highly restrictive sieve with respect to plasma proteins, thus modulating both interstitial protein concentration and transendothelial fluid filtration; (b) a mechanical support to lymphatic vessels sustaining and modulating their draining function, and (c) a rigid three-dimensional low-compliant scaffold opposing fluid accumulation into the interstitial space. Fragmentation of PG induced by increased plasma volume, by degradation through proteolytic or inflammatory agents, by exposure to inspiratory gas mixture with modified oxygen fraction, or by increased tissue strain/stress invariably results in the progressive loosening of PG intermolecular bonds with other ECM components. The loss of the PGs regulatory functions compromises the protective role of the tissue solid matrix progressively leading to interstitial and eventually severe lung edema. This article is discussed in the editorial available at:     

负荷改变对髁突骨上组织细胞及细胞外基质的影响—超微结构的研究

目的：检测髁状突骨上组织细胞及细胞外基质超微结构在负荷改变后的变化特点。方法：４只成年家兔在被拔除双侧下颌磨牙后１月和３月,用透射电镜的方法观察组织的表现。结果：细胞发生了不同程度的改建及退行性反应,如粗面内质网的扩张,线粒体肿胀,溶酶体增多等;基质中胶原原纤维的有序排列结构消失,胶原网受到破坏,同时蛋白多糖颗粒减少;基质中脂质小体及基质小囊等成分增多;负重区较非负重区的改变更显著。结论：过重的负荷会超过组织的代偿能力,使细胞产生基质的能力下降,对细胞自身产生不利的影响,引起髁状突的弹性及抗压、抗磨擦等能力的下降     

云芝多糖防止缺血再灌注心肌早期损伤

为了探讨云芝多糖对心肌缺血再灌注损伤的预防作用，制备犬心肌缺血再灌注损伤模型，输血再灌注组不用药物干预，云芝多糖组手术前2天每天口服云芝多糖150mg/kg。在缺血再灌注过程不同时间点测定左心室舒张压，超声心功能和冠状静脉窦血浆丙二醛浓度，心肌标本行透射电镜检查。结果发现，缺血再灌注组再灌注前和再灌注早期左心室舒张压显著升高，云芝多糖组仅再灌注前左心室舒张压升高，再灌注前两组缺血心肌节段收缩期增厚百分率显著下降，并表现为矛盾运动，再灌注期两组缺血心肌节段收缩期增厚百分率呈进行性改善，至再灌注120min两组均未恢复至结扎前水平，且云芝多糖组显著高于相应时间咪缺血再灌注组；左心室射血分数的变化趋势与缺血心肌节段收缩期增厚百分率相似，但恢复较快，云芝多糖组于再灌注90min即恢复至结扎前水平。缺血再灌注组再灌注期丙二醛浓度明显升高，至再灌注120min尚未恢复至结扎前水平。而云芝多糖组再灌注早期丙二醛浓度升高，但回降较快，于再灌注30min即恢复至结扎前水平，缺血再灌注组心肌组织水肿，心肌细胞少部分肌丝断裂，收缩带模糊，线粒体轻度肿胀，脱颗粒，胞质水肿；云芝多糖组心肌组织除轻微水肿外，未见其它明显结构改变，结果提示，云芝多糖对缺血再灌注早期心肌有显著保护作用。     

Thiazolidinediones reduce the LDL binding affinity of non-human primate vascular cell proteoglycans

Aims/hypothesis Retention of atherogenic lipoproteins in the artery wall by proteoglycans is a key step in the development of atherosclerosis. Thiazolidinediones have been shown to reduce atherosclerosis in mouse models. The aim of this study was to determine whether thiazolidinediones modify vascular proteoglycan synthesis in a way that decreases LDL binding.Methods Primate aortic smooth muscle cells were exposed to troglitazone or rosiglitazone, or no stimulus at all for a 24-hour steady-state labelling period. Sulphate incorporation, size and LDL binding affinity of proteoglycans were determined. Proteoglycans secreted by cells in the presence or absence of troglitazone were separated into large and small classes by size exclusion chromatography, and LDL binding affinity was determined.Results Proteoglycans synthesised by cells exposed to troglitazone or rosiglitazone were smaller, with decreased sulphate incorporation and decreased LDL binding affinity. However, troglitazone had a greater effect than rosiglitazone. Troglitazone reduced the LDL binding affinities of both the large and small proteoglycans compared with control. The binding differences persisted when glycosaminoglycan chains released from proteoglycans were incubated with LDL, indicating that troglitazone affects the glycosaminoglycan synthetic machinery of these cells.Conclusions/interpretation Thiazolidinediones decrease the LDL binding affinity of the proteoglycans synthesised by primate aortic smooth muscle cells. This could, in part, account for the reduced atherosclerosis observed in animal models.Abbreviations PPAR peroxisome proliferator-activated receptor - K_d binding constantPresented in part at the 3rd Annual Conference on Arteriosclerosis, Thrombosis and Vascular Biology, Salt Lake City, Utah, USA, 6 April 2002     

Biglycan protects cardiomyocytes against hypoxia/reoxygenation injury: Role of nitric oxide

Biglycan, a proteoglycan component of extracellular matrix, has been suspected to contribute to the development of atherosclerosis, but overexpression of biglycan in transgenic mice has been shown to induce cardioprotective genes including nitric oxide (NO) synthases in the heart. Therefore, here we hypothesized if exogenous administration of biglycan exerts cytoprotection. Primary cardiomyocytes from neonatal rats were subjected to 150 min hypoxia and 2 h reoxygenation. Mortality of cardiomyocytes was dose-dependently attenuated by pretreatment with 1-100 nM biglycan. Biglycan enhanced eNOS mRNA and protein, and significantly increased NO content of cardiomyocytes. The NO synthase inhibitor l-nitro-arginine-methyl-ester significantly attenuated the cytoprotective effect of biglycan. This is the first demonstration that biglycan leads to cytoprotection against hypoxia/reoxygenation injury, and that this phenomenon is partially mediated by an NO-dependent mechanism.     

实验性蛋白多糖降解致兔膝关节软骨早期退变的核磁共振成像研究

目的　探讨低场磁共振成像 (MRI)在检测骨关节炎 (OA)早期软骨退变的表现及其价值。方法　选用新西兰大白兔 32只 ,右侧膝关节腔内注射 0 1ml木瓜蛋白酶溶液 (5U) ,建立OA早期软骨退变的动物模型。并在注药前及注药后 2 4、4 8、72h行双侧膝关节矢状面GE准T2 WI、SE T1WI、SE PDWI、SE T2 WI序列成像 ,取关节软骨组织作蛋白多糖含量测定和组织病理学检查。结果　注射木瓜蛋白酶后 2 4、4 8h ,关节软骨明显变薄 ,磁共振 (MR)信号强度明显降低。与对照组比较 ,两者差异均有显著性 (P <0 0 5 )。至注药后 72h关节软骨的厚度及信号强度已基本恢复正常。与对照组比较 ,两者差异无显著性 (P >0 0 5 )。关节软骨蛋白多糖含量测定及组织学检查结果表明 ,注射木瓜蛋白酶后 2 4、4 8h ,蛋白多糖含量明显降低 ,至注药后 72h ,蛋白多糖含量已逐渐恢复。软骨细胞均未见异常改变。结论　通过MR检查 ,可发现早期的软骨退变。     

硫酸软骨素蛋白多糖与中枢神经系统可塑性

硫酸软骨素蛋白多糖(chondroitin sulfate proteoglycan,CSPG)是在发育和成熟的中枢神经系统(central nervous syste,CNS)中广泛表达的一组细胞外基质分子,在胚胎CNS发育和成年期CNS可塑性中发挥着重要作用.CSPG作为一种主要的细胞外抑制性成分,可影响CNS损伤后轴突再生和神经功能恢复.     

牛主动脉蛋白聚糖对培养的人主动脉平滑肌细胞生长的影响

为探讨蛋白聚糖在动脉粥样硬化发生发展中的作用,观察牛主动脉硫酸肝素蛋白聚糖、硫酸软骨素蛋白聚糖、硫酸皮肤－硫酸软骨素蛋白聚糖和三种蛋白聚糖的混合物对培养的人主动脉平滑肌细胞增殖的影响。用细胞计数计算硫酸肝素蛋白聚糖（１．５￣７．０ｍｇ／Ｌ）对培养的人主动脉平滑肌细胞增殖的抑制率分别为０．５５％和７６％;硫酸软骨素蛋白聚糖（１５．０￣６０．０ｍｇ／Ｌ）的抑制率分别为２３％、３４％和６５％;硫酸皮肤素