Aortic wall cell proliferation via basic fibroblast growth factor gene transfer limits progression of experimental abdominal aortic aneurysm
Aortic wall cell proliferation via basic fibroblast growth factor gene transfer limits progression of experimental abdominal aortic aneurysm
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DOI：
10.1016/j.jvs.2004.06.018
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发表时间：
2004-09-01
影响因子：
4.3
通讯作者：
Nagawa, H
中科院分区：
文献类型：
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作者：
Hoshina, K;Koyama, H;Nagawa, H
目的：我们之前的研究表明，高流量条件刺激腹主动脉瘤（AAA）大鼠模型中主动脉壁的细胞增殖，我们推测中膜细胞密度和主动脉壁完整性之间可能存在关系。在本研究中，我们提供了碱性成纤维细胞生长因子（bFGF）基因的大鼠腹主动脉瘤模型的主动脉壁，并评估了生长因子增强的平滑肌细胞（SMC）增殖对动脉瘤progress.Methods的影响：AAA诱导大鼠通过输注猪胰弹性蛋白酶。弹性蛋白酶灌注后立即用含有bFGF基因（bFGF组）或LacZ基因（对照组）的表达质粒载体填充腹主动脉;然后用体内电穿孔方法进行基因转移到主动脉壁。治疗后7天处死动物，测量动脉瘤。免疫组化法计数平滑肌细胞、巨噬细胞和内皮细胞数量，溴脱氧尿苷（BrdU）染色法检测细胞增殖。bFGF组的动脉瘤直径明显小于对照组（4.6 ± 0.3 mm vs 6.5 ± 1.4 mm; P <0.01）。bFGF组中膜平滑肌细胞数和BrdU掺入细胞数均显著高于对照组（SMC，101 +/- 34/高倍视野[hpf] vs 80 +/- 31/hpf; P <0.05，BrdU，107 +/- 63/hpf vs 50 +/- 33/hpf;而巨噬细胞和内皮细胞的数量在两组间无差异。将bFGF输送到主动脉壁诱导中膜SMC增殖显著增强，而不增加炎性浸润，然后成功限制动脉瘤扩大。这些结果表明，增加中膜细胞抑制动脉瘤的形成，这可能提供了一个线索，开发一个新的战略，治疗AAA。
Objective: Our previous study demonstrated that high flow conditions stimulated cell proliferation in the aortic wall in a rat model of abdominal aortic aneurysm (AAA), and we speculated that there is a possible relation between medial cell density and aortic wall integrity. In the present study we delivered the basic fibroblast growth factor (bFGF) gene to the aortic wall of a rat AAA model and evaluated the effects of growth factor-enhanced smooth muscle cell (SMC) proliferation on aneurysm progression.Methods: AAA was induced in rats by means of infusion of porcine pancreatic elastase. Immediately after elastase infusion the abdominal aorta was filled with an expression plasmid vector containing the bFGF gene (bFGF group) or LacZ gene (control group); then gene transfer to the aortic wall was carried out with an in vivo electroporation method. The animals were killed 7 days after treatment, and the aneurysm was measured. The numbers of SMCs, macrophages, and endothelial cells were counted with immunostaining, and cell replication was evaluated with bromodeoxyuridine (BrdU) staining.Results. Aneurysm diameter in the bFGF group was significantly smaller than that in the control group (4.6 +/- 0.3 mm vs 6.5 +/- 1.4 mm; P < .01). The numbers of medial SMCs and BrdU-incorporated cells in the bFGF group were significantly greater than those in the control group (SMC, 101 +/- 34 per high-power field [hpf] vs 80 +/- 31/hpf; P < .05, BrdU, 107 +/- 63/hpf vs 50 +/- 33/hpf; P < .05), whereas no difference was detected in the numbers of macrophages and endothelial cells between the 2 groups.Conclusions. Delivery of bFGF to the aortic wall induced significant enhancement of medial SMC proliferation, without an increase in inflammatory infiltration, then successfully limited aneurysm enlargement. These findings suggest that increased medial cellularity inhibits aneurysm formation, which possibly offers a clue for developing a new strategy for treatment of AAAs.