Department of Cardiovascular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK.
Eur Heart J. 2013 Nov;34(43):3378-88. doi: 10.1093/eurheartj/ehs240. Epub 2012 Sep 24.
Understanding endothelial cell repopulation post-stenting and how this modulates in-stent restenosis is critical to improving arterial healing post-stenting. We used a novel murine stent model to investigate endothelial cell repopulation post-stenting, comparing the response of drug-eluting stents with a primary genetic modification to improve endothelial cell function.
Endothelial cell repopulation was assessed en face in stented arteries in ApoE(-/-) mice with endothelial-specific LacZ expression. Stent deployment resulted in near-complete denudation of endothelium, but was followed by endothelial cell repopulation, by cells originating from both bone marrow-derived endothelial progenitor cells and from the adjacent vasculature. Paclitaxel-eluting stents reduced neointima formation (0.423 ± 0.065 vs. 0.240 ± 0.040 mm(2), P = 0.038), but decreased endothelial cell repopulation (238 ± 17 vs. 154 ± 22 nuclei/mm(2), P = 0.018), despite complete strut coverage. To test the effects of selectively improving endothelial cell function, we used transgenic mice with endothelial-specific overexpression of GTP-cyclohydrolase 1 (GCH-Tg) as a model of enhanced endothelial cell function and increased NO production. GCH-Tg ApoE(-/-) mice had less neointima formation compared with ApoE(-/-) littermates (0.52 ± 0.08 vs. 0.26 ± 0.09 mm(2), P = 0.039). In contrast to paclitaxel-eluting stents, reduced neointima formation in GCH-Tg mice was accompanied by increased endothelial cell coverage (156 ± 17 vs. 209 ± 23 nuclei/mm(2), P = 0.043).
Drug-eluting stents reduce not only neointima formation but also endothelial cell repopulation, independent of strut coverage. In contrast, selective targeting of endothelial cell function is sufficient to improve endothelial cell repopulation and reduce neointima formation. Targeting endothelial cell function is a rational therapeutic strategy to improve vascular healing and decrease neointima formation after stenting.
了解支架置入后内皮细胞再增殖情况，以及其如何调节支架内再狭窄，这对于改善支架置入后的动脉愈合至关重要。我们使用一种新型的小鼠支架模型来研究支架置入后的内皮细胞再增殖情况，比较了改善内皮细胞功能的药物洗脱支架与主要基因修饰的反应。
在载脂蛋白 E 基因敲除（ApoE(-/-)）小鼠中，使用内皮细胞特异性 LacZ 表达来评估支架内动脉的内皮细胞再增殖情况。支架置入导致内皮几乎完全剥脱，但随后内皮细胞再增殖，起源于骨髓源性内皮祖细胞和邻近血管的细胞。紫杉醇洗脱支架减少新生内膜形成（0.423±0.065 与 0.240±0.040mm²，P=0.038），但减少内皮细胞再增殖（238±17 与 154±22 核/mm²，P=0.018），尽管完全覆盖了支架。为了测试选择性改善内皮细胞功能的效果，我们使用内皮细胞特异性过表达 GTP-环化水解酶 1（GCH-Tg）的转基因小鼠作为增强内皮细胞功能和增加一氧化氮产生的模型。GCH-Tg 载脂蛋白 E 基因敲除（ApoE(-/-)）小鼠与载脂蛋白 E 基因敲除（ApoE(-/-)）同窝仔相比，新生内膜形成减少（0.52±0.08 与 0.26±0.09mm²，P=0.039）。与紫杉醇洗脱支架不同，GCH-Tg 小鼠的新生内膜形成减少伴随着内皮细胞覆盖增加（156±17 与 209±23 核/mm²，P=0.043）。
药物洗脱支架不仅减少新生内膜形成，还减少内皮细胞再增殖，而不依赖于支架覆盖率。相比之下，选择性针对内皮细胞功能足以改善内皮细胞再增殖并减少新生内膜形成。靶向内皮细胞功能是改善支架置入后血管愈合和减少新生内膜形成的合理治疗策略。
Zotero 插件
