VA Pittsburgh Healthcare System, Pittsburgh, PA 15240, USA.
Division of Vascular Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
Cells. 2021 Dec 21;11(1):7. doi: 10.3390/cells11010007.
When a large artery becomes occluded, hemodynamic changes stimulate remodeling of arterial networks to form collateral arteries in a process termed arteriogenesis. However, the structural changes necessary for collateral remodeling have not been defined. We hypothesize that deconstruction of the extracellular matrix is essential to remodel smaller arteries into effective collaterals. Using multiphoton microscopy, we analyzed collagen and elastin structure in maturing collateral arteries isolated from ischemic rat hindlimbs. Collateral arteries harvested at different timepoints showed progressive diameter expansion associated with striking rearrangement of internal elastic lamina (IEL) into a loose fibrous mesh, a pattern persisting at 8 weeks. Despite a 2.5-fold increase in luminal diameter, total elastin content remained unchanged in collaterals compared with control arteries. Among the collateral midzones, baseline elastic fiber content was low. Outward remodeling of these vessels with a 10-20 fold diameter increase was associated with fractures of the elastic fibers and evidence of increased wall tension, as demonstrated by the straightening of the adventitial collagen. Inhibition of lysyl oxidase (LOX) function with β-aminopropionitrile resulted in severe fragmentation or complete loss of continuity of the IEL in developing collaterals. Collateral artery development is associated with permanent redistribution of existing elastic fibers to accommodate diameter growth. We found no evidence of new elastic fiber formation. Stabilization of the arterial wall during outward remodeling is necessary and dependent on LOX activity.
当大动脉发生阻塞时，血液动力学变化会刺激动脉网络的重塑，形成侧支动脉，这个过程被称为动脉生成。然而，侧支重塑所需的结构变化尚未得到明确。我们假设细胞外基质的解构对于将较小的动脉重塑为有效的侧支是至关重要的。我们使用多光子显微镜分析了从缺血大鼠后肢分离的成熟侧支动脉中的胶原和弹性蛋白结构。在不同时间点收获的侧支动脉显示出直径的逐渐扩张，与内部弹性膜（IEL）明显重新排列成松散的纤维网有关，这种模式在 8 周时仍然存在。尽管管腔直径增加了 2.5 倍，但与对照动脉相比，侧支动脉中的总弹性蛋白含量保持不变。在侧支中轴区，基线弹性纤维含量较低。这些血管的向外重塑导致弹性纤维断裂，并出现明显的壁张力增加，表现为外膜胶原的变直，其直径增加了 10-20 倍。用β-氨基丙腈抑制赖氨酰氧化酶（LOX）功能会导致正在发育的侧支中 IEL 的严重碎裂或连续性完全丧失。侧支动脉的发育与现有弹性纤维的永久性重新分配以适应直径的增长有关。我们没有发现新的弹性纤维形成的证据。在向外重塑过程中，动脉壁的稳定是必要的，并且依赖于 LOX 活性。
