Clinical Research Unit, Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Scientific Research Center, Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Chongming Branch, Shanghai, China.
Biosci Trends. 2019 Nov 13;13(5):423-429. doi: 10.5582/bst.2019.01274. Epub 2019 Oct 30.
In-stent restenosis is highly related to the deposition of inflammatory extracellular matrix and the migration of endothelial and vascular smooth muscle cells. The miR-17/TIMP-1/interleukin pathway regulates vascular matrix remodeling and plays an important role in the inflammatory reaction. This study identified miR-17 and its related biomarkers in serum that potentially indicated susceptibility to in-stent restenosis (ISR) after coronary artery stenting. Subjects were 42 patients with single de novo coronary artery lesions who underwent regular coronary angiography one year after percutaneous coronary intervention. The clinical baseline information was recorded. Serum levels of biomarkers (including miR-17, TIMP-1, IL-6, IL-8, IL-2R, TNF-alpha, IL-10, and IL-1beta) were measured with real-time PCR or ELISA. Intergroup comparisons were used to compare patients with or without ISR. Compared to levels in the non-restenosis group, the serum miR-17 level was significantly higher (3.13 ± 0.22 vs. 1.06 ± 0.04, p < 0.01) and the serum TIMP-1 and IL-6 levels were significantly lower in the ISR group (TIMP-1: 0.33 ± 0.04 vs. 1.00 ± 0.05, p < 0.01; IL-6: 1.64 ± 0.18 vs. 3.52 ± 0.11, p < 0.01). Moreover, the levels of TIMP-1 and IL-6 decreased as the level of miR-17 increased. Spearman's correlation analysis indicated that the miR-17 level was inversely correlated with TIMP-1 and IL-6 levels. Findings suggest that an elevated level of miR-17 and decreased levels of TIMP-1 and IL-6 may be associated with the risk of ISR, which is in accordance with vascular matrix remodeling and an inflammatory reaction during the pathologic process of ISR. This study highlighted the potential for miR-17, TIMP-1, and IL-6 to serve as biomarkers for ISR.
支架内再狭窄与炎症细胞外基质的沉积以及内皮细胞和血管平滑肌细胞的迁移密切相关。miR-17/TIMP-1/白细胞介素通路调节血管基质重塑，在炎症反应中发挥重要作用。本研究鉴定了血清中的 miR-17 及其相关生物标志物，这些标志物可能提示经皮冠状动脉介入治疗后支架内再狭窄（ISR）的易感性。受试者为 42 例初次发生单支冠状动脉病变的患者，这些患者在经皮冠状动脉介入治疗 1 年后接受了常规冠状动脉造影。记录了临床基线信息。采用实时 PCR 或 ELISA 法检测生物标志物（包括 miR-17、TIMP-1、IL-6、IL-8、IL-2R、TNF-α、IL-10 和 IL-1β）的血清水平。采用组间比较的方法比较有或无 ISR 的患者。与无再狭窄组相比，ISR 组血清 miR-17 水平显著升高（3.13±0.22 比 1.06±0.04，p<0.01），TIMP-1 和 IL-6 水平显著降低（TIMP-1：0.33±0.04 比 1.00±0.05，p<0.01；IL-6：1.64±0.18 比 3.52±0.11，p<0.01）。此外，随着 miR-17 水平的升高，TIMP-1 和 IL-6 的水平降低。Spearman 相关分析表明，miR-17 水平与 TIMP-1 和 IL-6 水平呈负相关。结果提示，miR-17 水平升高及 TIMP-1 和 IL-6 水平降低可能与 ISR 风险相关，这与 ISR 病理过程中的血管基质重塑和炎症反应一致。本研究强调了 miR-17、TIMP-1 和 IL-6 作为 ISR 生物标志物的潜力。
