Vascular smooth muscle cell endovascular therapy stabilizes already developed aneurysms in a model of aortic injury elicited by inflammation and proteolysis
Vascular smooth muscle cell endovascular therapy stabilizes already developed aneurysms in a model of aortic injury elicited by inflammation and proteolysis
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DOI：
10.1097/01.sla.0000114131.79899.82
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发表时间：
2004-03-01
影响因子：
9
通讯作者：
Becquemin, JP
中科院分区：
文献类型：
--
作者：
Allaire, E;Muscatelli-Groux, B;Becquemin, JP
目的：探讨血管内平滑肌细胞(VSMC)接种对基质金属蛋白酶(MMPs)诱导的已形成动脉瘤的愈合和稳定性的促进作用。这种细胞缺陷可能是动脉瘤愈合能力差和不断扩大的原因。方法：将炎症和蛋白降解导致细胞外基质损伤的大鼠主动脉瘤异种移植物种植于同种VSMCs内，对照组仅接受培养液。结果：血管内注射后8周，动脉瘤直径进一步增大，由3.0±-0.3 mm增加到10.9±-6.5 mm(P=0.009)，中层弹性蛋白含量由36.5±-8.5%下降到5.2+/-5.5%(S；P=0.009)，而种子组上述指标基本保持稳定(36.5±-8.4%至31.6%+/-9.7%，P=0.22)。VSMC接种后，单核细胞浸润减少。基质金属蛋白酶-1、-3、-7、-9和-12mRNA的含量在接种后的病壁中急剧下降。与对照组相比，血管内膜中金属蛋白酶组织抑制因子-1、-2和-3mRNAs的表达增加了2-10个数量级。明胶酶谱显示种植组基质金属蛋白酶-9活性消失，反向酶谱显示基质金属蛋白酶组织抑制物-3活性明显升高。结论：VSMC血管内种植可恢复蛋白水解性损伤的细胞外基质的修复能力，并能阻止血管扩张。
Objective: To investigate the efficiency of endovascular smooth muscle cell (VSMC) seeding in promoting healing and stability in already-developed aneurysms obtained by matrix metalloproteases (MMPs)-driven injury.Summary Background Data: VSMCs are instrumental in arterial healing after injury and are in decreased number in arterial aneurysms. This cellular deficiency may account for poor healing capabilities and ongoing expansion of aneurysms.Methods: Aneurysmal aortic xenografts in rats displaying extracellular matrix injury by inflammation and proteolysis were seeded endoluminally with syngeneic VSMCs, with controls receiving culture medium only. Diameter, structure, and the destruction/reconstruction balance were assessed.Results: Eight weeks after endovascular infusion, aneurysmal diameter had increased further, from 3.0 +/- 0.3 mm to 10.9 +/- 6.5 mm (P = 0.009), and medial elastin content had decreased from 36.5 +/- 8.5 to 5.2 +/- 5.5 surface-percent (S%; P = 0.009) in controls, whereas these parameters remained stable in the seeded group (3.0 +/- 0.3 to 2.7 +/- 0.2 mm, P = 0.08; 36.5 +/- 8.4 to 31.6 +/- 9.7 S%, P = 0.22). VSMC seeding was followed by a decrease in mononuclear infiltration. MMP-1, -3, -7, -9, and -12 mRNA contents were sharply decreased in the diseased wall in response to seeding. Tissue inhibitor of metalloproteinase-1, -2, and -3 mRNAs in the intima were increased in a 2 to 10 magnitude in comparison with controls. Gelatin zymography showed the disappearance of MMP-9 activity and reverse zymography a strong increase in tissue inhibitor of metalloproteinase-3 activity in the seeded group. VSMC-seeded aneurysms were rich in collagen and lined with an endothelium instead of a thrombus in controls.Conclusions: VSMCs endovascular seeding restores the healing capabilities of proteolytically injured extracellular matrix in aneurysmal aortas, and stops expansion.