Biosynthesis, Remodeling, and Functions During Vascular Morphogenesis and Neovessel Stabilization
Biosynthesis, Remodeling, and Functions During Vascular Morphogenesis and Neovessel Stabilization
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发表时间：
2005
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通讯作者：
G. Davis;D. Senger
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作者：
G. Davis;D. Senger
细胞外基质(ECM)对血管生物学的各个方面都是至关重要的。内皮细胞(ECs)与支持细胞协同作用，形成富含层粘连蛋白的基底膜基质，提供结构和组织稳定性。在血管生成开始的过程中，这种基底膜基质被各种蛋白酶降解，其中膜型基质金属蛋白酶(MT-MMPs)尤为重要。随着血管生成的进行，ECM在支持涉及调控EC迁移、侵袭、增殖和生存的关键信号事件方面发挥重要作用。此外，临时ECM作为一种柔韧的支架，在远端ECs之间建立机械导向力，从而在没有细胞-细胞接触的情况下提供组织线索。最后，通过特定的整合素依赖的信号转导途径，ECM控制EC细胞骨架来协调血管形态发生的复杂过程，通过这个过程，增殖的EC组织成具有功能管腔的多细胞管。因此，ECM的组成以及ECM降解和重塑的调节在管腔和管的形成以及最终新生血管的稳定和成熟方面起着关键作用。(中国保监会决议2005；97：1093-1107。)
The extracellular matrix (ECM) is critical for all aspects of vascular biology. In concert with supporting cells, endothelial cells (ECs) assemble a laminin-rich basement membrane matrix that provides structural and organizational stability. During the onset of angiogenesis, this basement membrane matrix is degraded by proteinases, among which membrane-type matrix metalloproteinases (MT-MMPs) are particularly significant. As angiogenesis proceeds, ECM serves essential functions in supporting key signaling events involved in regulating EC migration, invasion, proliferation, and survival. Moreover, the provisional ECM serves as a pliable scaffold wherein mechanical guidance forces are established among distal ECs, thereby providing organizational cues in the absence of cell-cell contact. Finally, through specific integrin-dependent signal transduction pathways, ECM controls the EC cytoskeleton to orchestrate the complex process of vascular morphogenesis by which proliferating ECs organize into multicellular tubes with functional lumens. Thus, the composition of ECM and therefore the regulation of ECM degradation and remodeling serves pivotally in the control of lumen and tube formation and, finally, neovessel stability and maturation. (Circ Res. 2005;97:1093-1107.)