Hebei Medical University First Affiliated Hospital, Shijiazhuang 050023, Hebei, China.
Hebei Medical University Second Affiliated Hospital, Shijiazhuang 050023, Hebei, China.
Aging (Albany NY). 2022 Feb 24;14(4):1865-1878. doi: 10.18632/aging.203908.
microRNAs (miRNAs) have drawn more attention to the progression of atherosclerosis (AS), due to their noticeable inflammation function in cardiovascular disease. Macrophages play a crucial role in disrupting atherosclerotic plaque, thereby we explored the involvement of miR-223-3p in the inflammatory response in macrophages.
RT-qPCR was used to analyze the miR-223-3p levels in carotid arteries and serum of AS patients. ROC curve was used to assess the diagnostic value of miR-223-3p. Movat staining was applied to evaluate the morphological differences. FISH was used to identify the expression of miR-223-3p in macrophages of atherosclerotic lesions. Bioinformatic analysis was performed. Double-immunofluorescence and western blot were performed to assess the inflammatory cytokine secretion and p-ERK1/2. C16-PAF was injected into the culture medium of the miR-223-3p mimic/NC-transfected macrophages with ox-LDL.
MiR-223-3p was up-regulated in AS patients and was associated with a higher overall survival rate. MiR-223-3p was co-localized with CD68+ macrophages in vulnerable atherosclerotic lesions. MiR-223-3p mimics decreased atherosclerotic lesions, macrophages numbers whereas increased SMCs numbers in the lesions. The TNF-a immune-positive areas were reduced by miR-223-3p mimics. MAP2K1 was negatively associated with miR-223-3p. MiR-223-3p mimics reduced the inflammation and the MEK1/ERK1/2 signaling pathway and . C16-PAF reversed the effects of miR-223-3p mimics on inflammation and ERK1/2 signaling pathway.
MiR-223-3p negatively regulates inflammatory responses by the MEK1/ERK1/2 signaling pathway. Our study provides new insight into how miR-223-3p protects against atherosclerosis, representing a broader therapeutic prospect for treating atherosclerosis by miR-223-3p.
微小 RNA（miRNAs）因其在心血管疾病中的显著炎症功能而引起人们对动脉粥样硬化（AS）进展的更多关注。巨噬细胞在破坏动脉粥样硬化斑块中起着至关重要的作用，因此我们探讨了 miR-223-3p 在巨噬细胞炎症反应中的作用。
采用 RT-qPCR 分析 AS 患者颈动脉和血清中的 miR-223-3p 水平。ROC 曲线评估 miR-223-3p 的诊断价值。Movat 染色评估形态学差异。FISH 鉴定动脉粥样硬化病变中巨噬细胞的 miR-223-3p 表达。进行生物信息学分析。双免疫荧光和 Western blot 检测 ox-LDL 处理的 miR-223-3p 模拟物/NC 转染巨噬细胞的炎症细胞因子分泌和 p-ERK1/2。用 C16-PAF 处理 miR-223-3p 模拟物/NC 转染的巨噬细胞培养物中的 ox-LDL。
miR-223-3p 在 AS 患者中上调，并与较高的总生存率相关。miR-223-3p 与易损性动脉粥样硬化病变中的 CD68+巨噬细胞共定位。miR-223-3p 模拟物减少动脉粥样硬化病变中的巨噬细胞数量，增加病变中的平滑肌细胞数量。miR-223-3p 模拟物减少 TNF-a 免疫阳性面积。MAP2K1 与 miR-223-3p 呈负相关。miR-223-3p 模拟物减少炎症和 MEK1/ERK1/2 信号通路。C16-PAF 逆转 miR-223-3p 模拟物对炎症和 ERK1/2 信号通路的作用。
miR-223-3p 通过 MEK1/ERK1/2 信号通路负调控炎症反应。我们的研究为 miR-223-3p 如何保护动脉粥样硬化提供了新的见解，代表了通过 miR-223-3p 治疗动脉粥样硬化的更广泛的治疗前景。
