miR-146a 通过靶向 CARD10 调节腹主动脉瘤患者的炎症和发展。
miR-146a regulates inflammation and development in patients with abdominal aortic aneurysms by targeting CARD10.
机构信息
Department of Vascular Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China.
Department of Vascular Surgery, The First Affiliated Hospital of Kunming Medical University, Kunming Medical University, Kunming, China -
出版信息
Int Angiol. 2020 Aug;39(4):314-322. doi: 10.23736/S0392-9590.20.04283-2. Epub 2020 Mar 4.
BACKGROUND
We present the expression of miR-146a in abdominal aortic aneurysms (AAA) patients, and its mechanism for regulating inflammation and development in AAA patients.
METHODS
The expression of miR-146a in serum, PBMC, and abdominal aorta tissues was measured in AAA patients.
RESULTS
We found that level of miR-146a in the serum and its expression in AAA tissues were significantly higher than that in healthy people or normal abdominal aorta tissues. Pearson's method analysis showed that miRNA-146a in the serum of AAA patients was negatively correlated with serum TNF-α, IFN-γ and CRP, and was positively correlated with serum IL-10. The luciferase reporter gene system confirmed that miR-146a targeted inhibition of CARD10 expression in THP-1 and human umbilical vein endothelial cells (HUVECs), and miR-146a was negatively correlated with the expression of CARD10 in the tissues/PBMC of AAA patients. In PBMC of healthy people, over-expression of miR-146a by transferring miR-146a-mimic could increase the expression of SIRT1 but decreased the expression of p65 and the level of TNF-α secretion. Moreover, HUVECs cellular activity change by TNF-α in a dose-dependent manner.
CONCLUSIONS
These results suggested that miR-146a suppressed the inflammation of peripheral blood in AAA patients by targeting CARD10, and miR-146a blocked the progression of AAA through CARD10/SIRT1/p65 pathway.
背景
我们展示了 miR-146a 在腹主动脉瘤（AAA）患者中的表达，及其在 AAA 患者中调节炎症和发展的机制。
方法
测量了 AAA 患者血清、PBMC 和腹主动脉组织中 miR-146a 的表达。
结果
我们发现，血清中 miR-146a 的水平及其在 AAA 组织中的表达均明显高于健康人群或正常腹主动脉组织。Pearson 方法分析表明，AAA 患者血清中的 miRNA-146a 与血清 TNF-α、IFN-γ 和 CRP 呈负相关，与血清 IL-10 呈正相关。荧光素酶报告基因系统证实，miR-146a 靶向抑制 THP-1 和人脐静脉内皮细胞（HUVEC）中的 CARD10 表达，并且 miR-146a 与 AAA 患者组织/PBMC 中 CARD10 的表达呈负相关。在健康人群的 PBMC 中，通过转染 miR-146a-mimic 过表达 miR-146a 可以增加 SIRT1 的表达，同时降低 p65 的表达和 TNF-α 分泌水平。此外，HUVECs 的细胞活性随 TNF-α 的剂量依赖性变化。
结论
这些结果表明，miR-146a 通过靶向 CARD10 抑制 AAA 患者外周血中的炎症，并且 miR-146a 通过 CARD10/SIRT1/p65 通路阻断 AAA 的进展。
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