Eble Johannes A, Niland Stephan
Center for Molecular Medicine, Dept. Vascular Matrix Biology, Excellence Cluster Cardio-Pulmonary System, Frankfurt University Hospital, 60590 Frankfurt, Germany.
Curr Pharm Des. 2009;15(12):1385-400. doi: 10.2174/138161209787846757.
Blood vessels are highly organized and complex structure, which are far more than simple tubes conducting the blood to almost any tissue of the body. They are able to autonomously regulate the blood flow, thus providing the tissues an optimal support of oxygen and nutrients and an efficient removal of waste products. In higher organisms, the blood vessel forms a closed circuit system, which additionally has the ability to seal itself in case of leakage as a result of injury. The blood vessel system does not only transport soluble substances, but also serves as "highway" system for leukocytes to patrol the body during the immunological surveillance and to reach the inflammation site quickly. In a complex interplay with the vascular wall, leukocytes are able to penetrate the blood vessel without any obvious leakage. Pathologically, tumor cells subvert the blood vessel system to disseminate from the primary tumor and colonize distant organs during metastasis. The extracellular matrix (ECM) of a blood vessel contributes substantially to the diverse functions of the blood vessel. First, the ECM constitutes the scaffold which keeps the histological structure of the vessel wall in shape but also bears the enormous and permanent mechanical forces levied on the vessel by the pulsatile blood flow in the arteries and by vasoconstriction, which regulates blood flow and pressure. The complex network of elastic fibers and tensile forces-bearing networks are well adapted to accomplish these mechanical tasks. Second, the ECM provides informational cues to the vascular cells, thus regulating their proliferation and differentiation. Third, ECM molecules can store, mask, present or sequester growth factors, thereby modulating their effects remarkably. Furthermore, several ECM molecules serve additional functions within the blood vessel. Their expression is altered in a spatial and temporal pattern during blood vessel formation and remodeling. In contrast to vasculogenesis during embryonic development, blood vessel shows a remarkably and life-long plasticity, which allows the formation and regeneration of new blood vessel even in adulthood. Both physiologically during wound healing and pathologically during tumor growth, the sprouting of new blood vessels during angiogenesis is an important process, in which the ECM takes a key role.
血管是高度有组织且复杂的结构,远不止是将血液输送到身体几乎任何组织的简单管道。它们能够自主调节血流,从而为组织提供氧气和营养物质的最佳支持,并有效清除废物。在高等生物中,血管形成一个封闭的循环系统,在因受伤而发生渗漏时,该系统还具有自我封闭的能力。血管系统不仅运输可溶性物质,还作为白细胞的“高速公路”系统,使其在免疫监视期间巡逻身体并迅速到达炎症部位。在与血管壁的复杂相互作用中,白细胞能够穿透血管而无明显渗漏。在病理情况下,肿瘤细胞会颠覆血管系统,以便在转移过程中从原发性肿瘤扩散并在远处器官定植。血管的细胞外基质(ECM)对血管的多种功能有重要贡献。首先,ECM构成支架,保持血管壁的组织结构完整,同时承受动脉中脉动血流和调节血流与压力的血管收缩对血管施加的巨大且持久的机械力。弹性纤维和承受拉力网络的复杂网络非常适合完成这些机械任务。其次,ECM为血管细胞提供信息线索,从而调节它们的增殖和分化。第三,ECM分子可以储存、掩盖、呈递或隔离生长因子,从而显著调节它们的作用。此外,几种ECM分子在血管内还具有其他功能。它们的表达在血管形成和重塑过程中呈时空模式变化。与胚胎发育期间的血管生成不同,血管具有显著且终身的可塑性,这使得即使在成年期也能形成和再生新血管。无论是在伤口愈合的生理过程中,还是在肿瘤生长的病理过程中,血管生成过程中新血管的萌发都是一个重要过程,其中ECM起着关键作用。