Highly Purified Eicosapentaenoic Acid Alleviates the Inflammatory Response and Oxidative Stress in Macrophages during Atherosclerosis via the miR-1a-3p/sFRP1/Wnt/PCP-JNK Pathway

Abstract

Highly purified eicosapentaenoic acid (EPA) has shown great effects in the prevention of atherosclerosis. In a murine model, it significantly reduced plaque accumulation, lowered plasma lipid levels, and decreased inflammation levels, which was also observed in vitro. Using microRNA sequencing, we identified differentially expressed microRNAs, among which miR-1a-3p was selected for further validation. Overexpression of miR-1a-3p in RAW264.7 cells worsened lipid accumulation, increased oxidative stress, and exacerbated inflammatory responses whereas its downregulation produced the opposite results. Potential targets of miR-1a-3p were analyzed by prediction tools. Then, secreted frizzled-related protein 1 (sFRP1), an antagonist of the Wnt pathway, was confirmed as the target gene of miR-1a-3p by a dual-luciferase reporter assay. Further research showed that in macrophages, EPA influenced the activation of the Wnt/planar cell polarity-c-Jun N-terminal kinase (Wnt/PCP-JNK) axis, which is consistent with the phenomenon that miR-1a-3p has an impact on this same axis. Collectively, our findings suggest that EPA mitigates inflammatory responses and oxidative responses both in vivo and in vitro by targeting the miR-1a-3p/sFRP1/Wnt/PCP-JNK axis in macrophages, which may explain the cardioprotective role of EPA and promote the application of EPA in clinical practice.

Tanshinone IIA is superior to paricalcitol in ameliorating tubulointerstitial fibrosis through regulation of VDR/Wnt/β-catenin pathway in rats with diabetic nephropathy

“…Wnt/β-catenin signaling pathway plays an important role in vascular diseases such as myocardial infarction (He et al 2022 ), atherosclerosis (Zang et al 2022 ), cardiovascular calcification (Wang et al 2019 ), and diabetic retinopathy [44[. Besides, the activation of Wnt/β-catenin pathway when EMT and TIF occur has been proved in a lupus nephritis model (Fu et al 2019 ).…”

Fatty acids in cancer: Metabolic functions and potential treatment

“…As described above, lipids can not only provide energy for cellular activities and material basis for cell proliferation but also act as messengers to transmit intercellular and intracellular signals. Eicosanoids, sphingolipids, and phosphoinositides are all signaling lipids 105–108 . Here, we focus on a class of signaling lipids directly synthesized by FAs, namely eicosanoids.…”

“…Eicosanoids are the major signaling lipids, and most of them have procancer effects, such as PGE 2 , LTB 4 , 20‐HETE, and 14,15‐EET 119,121,127,128 . Meanwhile, some eicosanoids can also play an antitumor role, such as PGD 2 , PGI 2 , and EDP 107,108 . In addition, the expression levels of metabolic enzymes that synthesize eicosanoids are also inconsistent in different tumors.…”

“…Eicosanoids, sphingolipids, and phosphoinositides are all signaling lipids. [105][106][107][108] Here, we focus on a class of signaling lipids directly synthesized by FAs, namely eicosanoids. Eicosanoids are a large class of bioactive signaling lipids produced by the metabolism of 20-carbon PUFA.…”

“…119,121,127,128 Meanwhile, some eicosanoids can also play an antitumor role, such as PGD 2 , PGI 2 , and EDP. 107,108 In addition, the expression levels of metabolic enzymes that synthesize eicosanoids are also inconsistent in different tumors. For instance, 15-LOX-1, an enzyme involved in LTs synthesis, has been reported as a cancer suppressor in colon cancer, but a cancer promoter in prostate cancer.…”