Sex differences in arterial identity correlate with neointimal hyperplasia after balloon injury.

Sex differences in arterial identity correlate with neointimal hyperplasia after balloon injury.
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动脉身份的性别差异与球囊损伤后的新内膜增生相关。

DOI:
10.1007/s11033-022-07644-2
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发表时间:
2022-09
影响因子:
2.8
通讯作者:
Dardik, Alan
Dardik, Alan
中科院分区:
生物学4区
文献类型:
--
作者:
Gao, Mingjie;Gao, Xixiang;Taniguchi, Ryosuke;Brahmandam, Anand;Matsubara, Yutaka;Liu, Jia;Liu, Hao;Zhang, Weichang;Dardik, Alan

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动脉粥样硬化性动脉疾病的血管内治疗在临床结果(包括再狭窄)方面表现出性别差异。然而,尚未描述动脉重塑过程中动脉特性的性别特异性差异。我们假设,在新生内膜增殖和动脉重塑过程中,动脉决定子促红细胞生成素生成肝细胞受体相互作用蛋白 (Ephrin)-B2 的表达存在性别差异。在未进行性腺切除术或性腺切除术后 14 天对雌性和雄性 Sprague-Dawley 大鼠进行颈动脉球囊损伤;左颈总动脉受伤,同一动物的右颈动脉用作未受伤的对照。在手术前和手术后第 7 天和第 14 天使用超声检查对动脉血流动力学进行体内评估,并在球囊损伤后第 14 天使用组织学、免疫荧光和蛋白质印迹检查血管壁成分。没有显着的基线性别差异。球囊损伤后 14 天,雌性大鼠的新生内膜厚度减少,平滑肌细胞增殖减少,I 型和 III 型胶原沉积减少,TNFα 或 iNOS 阳性 CD68+ 细胞减少,CD206- 或 TGM2 阳性 CD68+ 细胞增加。雌性大鼠还表现出 VEGF-A、NRP1、磷酸化 EphrinB2 和 Notch1 增加的免疫反应性,以及磷酸化 Akt1、p38 和 ERK1/2 的减少。这些差异在接受性腺切除术预处理的大鼠中不存在。颈动脉球囊损伤后雌性大鼠新生内膜厚度的减少与动脉特性的改变有关,而动脉特性的改变依赖于完整的性激素。动脉特性的改变可能是动脉损伤后新内膜增殖性别差异的机制。在线版本包含可在 10.1007/s11033-022-07644-2 获取的补充材料。
Endovascular treatment of atherosclerotic arterial disease exhibits sex differences in clinical outcomes including restenosis. However, sex-specific differences in arterial identity during arterial remodeling have not been described. We hypothesized that sex differences in expression of the arterial determinant erythropoietin-producing hepatocellular receptor interacting protein (Ephrin)-B2 occur during neointimal proliferation and arterial remodeling. Carotid balloon injury was performed in female and male Sprague–Dawley rats without or 14 days after gonadectomy; the left common carotid artery was injured and the right carotid artery in the same animal was used as an uninjured control. Arterial hemodynamics were evaluated in vivo using ultrasonography pre-procedure and post-procedure at 7 and 14 days and wall composition examined using histology, immunofluorescence and Western blot at 14 days after balloon injury. There were no significant baseline sex differences. 14 days after balloon injury, there was decreased neointimal thickness in female rats with decreased smooth muscle cell proliferation and decreased type I and III collagen deposition, as well as decreased TNFα- or iNOS-positive CD68+ cells and increased CD206− or TGM2-positive CD68+ cells. Female rats also showed less immunoreactivity of VEGF-A, NRP1, phosphorylated EphrinB2, and increased Notch1, as well as decreased phosphorylated Akt1, p38 and ERK1/2. These differences were not present in rats pretreated with gonadectomy. Decreased neointimal thickness in female rats after carotid balloon injury is associated with altered arterial identity that is dependent on intact sex hormones. Alteration of arterial identity may be a mechanism of sex differences in neointimal proliferation after arterial injury. The online version contains supplementary material available at 10.1007/s11033-022-07644-2.
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