Davies M G, Fulton G J, Svendsen E, Hagen P O
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Cardiovasc Pathol. 1999 May-Jun;8(3):161-8. doi: 10.1016/s1054-8807(98)00029-5.
A previous study in which vein grafts were removed from the arterial circulation and reimplanted into the venous circulation of the same animal demonstrated regression of vein graft intimal hyperplasia and medial thickening within 14 days. The present study was designed to characterize the kinetics of the morphological and ultrastructural changes over this 14-day period. Twenty-one male New Zealand White rabbits received a reversed vein interposition bypass graft of the right common carotid artery. Fourteen days after the procedure, 21 vein grafts were isolated, removed, and reimplanted into the contralateral external jugular venous system as veno-venous interposition bypass grafts (reversal grafts). The grafts were harvested at 60 minutes, 1 day, 3 days, 5 days, 7 days, and 14 days after reversal. Before insertion into the venous circulation, the vein graft had a confluent endothelial cell surface with multiple layers of smooth muscle cells representing intimal hyperplasia. After 1 hour, the reversal graft retained an intact endothelial cell layer with no evidence of tissue edema or cellular disruption. By 24 hours, there were a few blood cells on the endothelial cell surface. There was no inflammatory infiltrate seen in the subendothelium, and the smooth muscle cells were unaltered. At 3 days, the endothelial cell lining remained intact with no polymorphonucleocytes in the subendothelium or within the graft wall. Underlying smooth muscle cells at this time were noted to contain cytoplasmic vacuoles. At 5 days, there were no inflammatory cells seen on the surface or within the vein graft wall, but many of the underlying smooth muscle cells within the intimal hyperplasia were noted to be fragmented and to have clumping of chromatin. After 7 days, the endothelial cells remained intact and there was widespread evidence of apoptosis beneath the subendothelium with highly fragmented smooth muscle cells, some of which were histologically in the process of breaking up. At 14 days, the grafts retained uniform endothelial cell surfaces. Most of the smooth muscle cells that composed the intimal hyperplasia seen before implantation as a reversal graft were gone. Areas of newly laid down collagen could be observed. There were no acute inflammatory cells but for some mast cells seen in the graft wall. This study demonstrates that in this model, regression of intimal hyperplasia was associated with apoptosis of the smooth muscle cells and the deposition of collagen. There was no evidence that this process is mediated by an acute inflammatory response. Regression therefore appears to be due to induction of smooth muscle cell apoptosis by either a reduction in pressure or flow or a combination of both factors. The findings will enable a systematic cellular and molecular analysis of the biology of regression, which may afford clues to better understand the biology of the developing intimal hyperplasia.
先前的一项研究将静脉移植物从动脉循环中取出，再植入同一动物的静脉循环，结果显示静脉移植物内膜增生和中层增厚在14天内出现消退。本研究旨在描述这14天内形态学和超微结构变化的动力学过程。21只雄性新西兰白兔接受了右颈总动脉的静脉倒置搭桥移植术。术后14天，分离出21个静脉移植物，取出后作为静脉-静脉间置搭桥移植物（反转移植物）再植入对侧颈外静脉系统。在反转后60分钟、1天、3天、5天、7天和14天采集移植物。在插入静脉循环之前，静脉移植物的内皮细胞表面融合，有多层平滑肌细胞，代表内膜增生。1小时后，反转移植物保留完整的内皮细胞层，没有组织水肿或细胞破坏的迹象。到24小时时，内皮细胞表面有一些血细胞。在内皮下未见炎性浸润，平滑肌细胞未改变。3天时，内皮细胞内衬保持完整，内皮下或移植物壁内没有多形核细胞。此时注意到下层平滑肌细胞含有细胞质空泡。5天时，在静脉移植物表面或壁内未见炎性细胞，但在内膜增生内的许多下层平滑肌细胞被发现破碎且染色质凝集。7天后，内皮细胞保持完整，在内皮下广泛存在凋亡证据，平滑肌细胞高度破碎，其中一些在组织学上正处于解体过程中。14天时，移植物保留均匀的内皮细胞表面。作为反转移植物植入前可见的构成内膜增生的大多数平滑肌细胞消失了。可以观察到新沉积胶原的区域。除了在移植物壁中看到一些肥大细胞外，没有急性炎性细胞。本研究表明，在该模型中，内膜增生的消退与平滑肌细胞凋亡和胶原沉积有关。没有证据表明这个过程是由急性炎症反应介导的。因此，消退似乎是由于压力或血流减少或两者共同作用诱导平滑肌细胞凋亡所致。这些发现将有助于对消退生物学进行系统的细胞和分子分析，这可能为更好地理解内膜增生发展的生物学特性提供线索。
