Department of Surgery, Section of Vascular Surgery and Endovascular Therapy, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de Mexico, Mexico.
Laboratory of Translational Medicine, National Institute of Cancerology, Ciudad de Mexico, Mexico.
Vascular. 2024 Aug;32(4):842-849. doi: 10.1177/17085381231162160. Epub 2023 Mar 13.
Intimal hyperplasia is the response to endothelial injury. Platelet-derived growth factor is released early and favors the formation of intimal hyperplasia. Although multiple treatments, from open surgery to endovascular techniques, have been used they remain controversial. There is currently interest in developing pharmacological strategies to address this pathology. Local vascular inflammation induced by vessel barotrauma generates intimal hyperplasia due to mechanical stress over the venous endothelium. Cilostazol is a selective phosphodiesterase type 3 (PDE3) selective inhibitor with a regulatory effect over intimal hyperplasia. The objective was to investigate cilostazol's role in inhibiting smooth muscle cell proliferation due to changes in the expression and release of PDGF-BB isoform and the effect on developing IH using an experimental model of vascular barotrauma (balloon-induced injury model).
We included 12 New Zealand rabbits. The balloon-induced injury model (BIIM) and experimental group cilostazol (20 mg/kg/day) included 6 rabbits each. Contralateral veins from 6 rabbits used in BIIM model has been taken as control group. We measured and compared the expression of PDGF-BB and the development of IH. A pathologist board chooses a PDGFRα antibody to localized its expression by immunohistochemistry analysis. Subsequently, using an automated immunohistochemical staining machine, the PDGFR expression was evaluated using a Zeiss Primo Star 4 light microscope.
The measurement obtained in the intimal layer was: 126.12 μm2 in the CG, 232 μm2 in the BIIM group, and 178 μm2 in the EG. A statistically significant difference was observed. Baseline serum concentrations of PDGF-BB in the BIIM group were 0.22 pg/mL. At 12 h 0.42 pg/mL, and 0.17 pg/mL at seven days. In the experimental group, the basal levels were 0.33 pg/mL. With the use of cilostazol, a lower peak was obtained at 12 h (0.08 pg/mL). This difference was statistically significant.
Cilostazol induced a significant reduction of IH caused by barotrauma in the venous endothelium, which correlates with decrease in the PDGF-BB in serum. This could be attributed to the pharmacologic effect on PDGFR expression.
内膜增生是对血管内皮损伤的反应。血小板衍生生长因子（PDGF）在早期释放，有利于内膜增生的形成。尽管已经使用了多种治疗方法，包括开放手术和血管内技术，但它们仍然存在争议。目前人们对开发治疗这种病理学的药物治疗策略感兴趣。由于静脉内皮的机械压力，血管壁创伤引起的局部血管炎症会导致内膜增生。西洛他唑是一种选择性磷酸二酯酶 3（PDE3）抑制剂，对内膜增生有调节作用。目的是研究西洛他唑在抑制血管壁创伤（球囊损伤模型）引起的平滑肌细胞增殖中的作用，以及通过改变 PDGF-BB 同工型的表达和释放对 IH 的影响。
我们纳入了 12 只新西兰兔。球囊诱导损伤模型（BIIM）和西洛他唑实验组（20mg/kg/天）各有 6 只兔子。BIIM 模型中对侧静脉作为对照组，共 6 只兔子。我们测量和比较了 PDGF-BB 的表达和 IH 的发展。病理学家小组选择 PDGFRα 抗体通过免疫组织化学分析来定位其表达。随后，使用自动免疫组织化学染色机，使用蔡司 Primo Star 4 光学显微镜评估 PDGFR 表达。
内膜层的测量结果为：CG 组为 126.12μm2，BIIM 组为 232μm2，EG 组为 178μm2。差异有统计学意义。BIIM 组血清 PDGF-BB 的基础浓度为 0.22pg/mL。12 小时时为 0.42pg/mL，7 天时为 0.17pg/mL。实验组基础水平为 0.33pg/mL。使用西洛他唑后，12 小时时的峰值较低（0.08pg/mL）。差异有统计学意义。
西洛他唑可显著减少静脉内皮引起的血管壁创伤性 IH，这与血清 PDGF-BB 降低有关。这可能归因于对 PDGFR 表达的药物作用。
