Darsaut T, Salazkin I, Ogoudikpe C, Gevry G, Bouzeghrane F, Raymond J
Research Centre, Notre-Dame Hospital, Montreal, Canada - Department of Surgery, Division of Neurosurgery, University of Alberta, Edmonton, Canada -
Interv Neuroradiol. 2006 Dec 15;12(4):289-302. doi: 10.1177/159101990601200401. Epub 2007 Jan 19.
Intracranial stents are increasingly used in the endovascular treatment of aneurysms, but very little is known regarding their effect on the cellular and molecular evolution of aneurysms. Bilateral venous pouch lateral wall carotid aneurysms were created in 20 dogs. All dogs then underwent angiography and balloon-expandable stenting of one aneurysm four to six weeks later. Fifteen dogs underwent aneurysm harvesting at one day (n=3), four days (n=4), seven days (n=3), and 14 days (n=5) for mRNA expression analysis, using axial sections taken from the aneurysm neck and fundus for RTPCR amplification of four cytokines or growth factors: TNF-a, TGF-b1, MCP-1, and PDGFBB; two adhesion molecules: VCAM-1 and PECAM-1; five matrix modifying agents; MMP- 2, 9, TIMPs 1, 3, 4, and two cellular markers: CD34 and a-SMA. Five other dogs, sacrificed at 12 weeks, were examined for extent of filling of the aneurysm neck with organized tissue and for neointima formation at the aneurysm ostium. Angiography was performed prior to sacrifice in all animals, and compared with initial studies. Eleven out of 20 stented aneurysms showed a favorable angiographic evolution, while none of the 20 nonstented aneurysms improved (p=0.001). Pathology showed partially occluded aneurysms, with neointima formation around the stent struts.Observed trends in mRNA expression, that stenting increased expression of genes involved in organization and neointima formation, agreed with experimental hypotheses, but differences between stented and non-stented aneurysms did not reach statistical significance. Parent vessel stenting was associated with angiographic improvement of aneurysm appearance. Modifications in mRNA expression patterns following stenting deserve further study to better establish potential molecular targets to promote aneurysm healing.
颅内支架在动脉瘤的血管内治疗中应用越来越广泛,但对于其对动脉瘤细胞和分子演变的影响却知之甚少。在20只犬身上制造双侧静脉袋侧壁颈动脉动脉瘤。然后所有犬均接受血管造影,4至6周后对其中一个动脉瘤进行球囊扩张支架置入。15只犬在术后1天(n = 3)、4天(n = 4)、7天(n = 3)和14天(n = 5)进行动脉瘤取材,用于mRNA表达分析,从动脉瘤颈部和底部获取轴向切片,通过RT-PCR扩增四种细胞因子或生长因子:TNF-α、TGF-β1、MCP-1和PDGF-BB;两种黏附分子:VCAM-1和PECAM-1;五种基质修饰剂:MMP-2、9、TIMP-1、3、4,以及两种细胞标志物:CD34和α-SMA。另外5只在12周时处死的犬,检查动脉瘤颈部被有组织的组织填充的程度以及动脉瘤开口处的新生内膜形成情况。所有动物在处死前均进行血管造影,并与初始研究进行比较。20个置入支架的动脉瘤中有11个显示出良好的血管造影演变,而20个未置入支架的动脉瘤均无改善(p = 0.001)。病理学显示动脉瘤部分闭塞,支架支柱周围有新生内膜形成。观察到的mRNA表达趋势,即支架置入增加了参与组织化和新生内膜形成的基因表达,与实验假设一致,但置入支架和未置入支架的动脉瘤之间的差异未达到统计学意义。母血管支架置入与动脉瘤外观的血管造影改善相关。支架置入后mRNA表达模式的改变值得进一步研究,以更好地确定促进动脉瘤愈合的潜在分子靶点。