Department of Cardiovascular Medicine, Jinan Central Hospital Affiliated to Shandong University, Jinan, Shandong 250013, P.R. China.
Department of Cardiology, Shandong University, Cheeloo College of Medicine, Jinan, Shandong 250013, P.R. China.
Mol Med Rep. 2017 Nov;16(5):6128-6133. doi: 10.3892/mmr.2017.7365. Epub 2017 Aug 28.
Previous studies including some vivo experiments and large scale clinical trials have indicated that angiopoietin like 4 (ANGPTL4) is involved in atherosclerosis. However, the specific mechanism underlying the process remains unresolved. Similarly, cumulative evidence indicated that hydrogen peroxide (H2O2) is closely related to the occurrence and development of atherosclerosis. The current study investigated whether H2O2 treatment can affect ANGPTL4 release in macrophage cells cell viability assay, western blot analysis, ELISA and immunofluorescence. It was determined that treatment with 0.25 and 0.5 mM H2O2 resulted in a significant increase in ANGPTL4 protein expression in macrophage cells. Mitogen‑activated protein kinase (MAPK) pathways were implicated in the secretion of ANGPTL4 regulated by H2O2, and specific inhibitors of MAPK1 (also known as ERK) and p38 MAPK significantly decreased H2O2 induced ANGPTL4 protein expression. Accordingly, it was demonstrated that ANGPTL4 expression was regulated by H2O2 via ERK and p38 MAPK, but not the MAPK8 (also known as JNK) pathway. In view of the effects of H2O2 and ANGPTL4 on atherosclerosis, the influence of H2O2 on ANGPTL4 provided new insight into the mechanism of atherosclerosis.
先前的研究包括一些体内实验和大规模临床试验表明,血管生成素样蛋白 4(ANGPTL4)参与动脉粥样硬化的形成。然而,这一过程的确切机制仍未解决。同样,越来越多的证据表明,过氧化氢(H2O2)与动脉粥样硬化的发生和发展密切相关。本研究探讨了 H2O2 处理是否会影响巨噬细胞细胞活力测定、western blot 分析、ELISA 和免疫荧光中 ANGPTL4 的释放。结果表明,用 0.25 和 0.5 mM H2O2 处理可显著增加巨噬细胞中 ANGPTL4 蛋白的表达。丝裂原激活的蛋白激酶(MAPK)途径参与 H2O2 调节的 ANGPTL4 分泌,MAPK1(也称为 ERK)和 p38 MAPK 的特异性抑制剂可显著降低 H2O2 诱导的 ANGPTL4 蛋白表达。因此,证明 ANGPTL4 的表达受 H2O2 通过 ERK 和 p38 MAPK 调节,而不是 MAPK8(也称为 JNK)途径。鉴于 H2O2 和 ANGPTL4 对动脉粥样硬化的影响,H2O2 对 ANGPTL4 的影响为动脉粥样硬化的机制提供了新的见解。