Dataset Information

Danlou Tablets Inhibit Atherosclerosis in Apolipoprotein E-Deficient Mice by Inducing Macrophage Autophagy: The Role of the PI3K-Akt-mTOR Pathway.

ABSTRACT: Atherosclerosis (AS) is a type of chronic vascular disease, and its etiology is not yet fully understood. AS is characterized by lipid deposition, atherosclerotic plaque formation, vascular stenosis or even complete blockage of the blood vessel wall. Clinical studies have shown that Danlou tablets (DLTs) can improve the heart function, quality of life, and prognosis of patients with coronary heart disease and myocardial infarction. However, its mechanism of action remains unknown. Our study revealed that DLTs ameliorated ApoE^-/-AS mouse aortic atherosclerotic plaques [hematoxylin-eosin (HE) staining and small animal ultrasound] and reduced CD68⁺ macrophage infiltration, the expression of the inflammatory factor interferon-gamma (IFN-γ), vascular smooth muscle α-actin, and serum lipid levels. In vitro, in the macrophage foaming model, DLTs partially restored the activity of RAW264.7 cells, reduced the uptake of lipid droplets, and inhibited lipid droplet accumulation and apoptosis within BMDMs. We also found that Torin1, an autophagy agonist, reduced intracellular lipid deposition in BMDMs, as did DLTs. Moreover, DLTs upregulated the expression of the autophagy-related protein LC3II and decreased p62 accumulation in RAW264.7 cells. DLTs also inhibited the phosphorylation of p-PI3K, p-Akt, and p-mTOR, leading to upregulated autophagy in RAW264.7 cells. In summary, our results suggested that DLTs can promote autophagy in macrophages by inhibiting the PI3K/Akt/mTOR signaling pathway, thereby reducing foam cell formation and improving atherosclerosis.

SUBMITTER: Liu C

PROVIDER: S-EPMC8455997 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Danlou Tablets Inhibit Atherosclerosis in Apolipoprotein E-Deficient Mice by Inducing Macrophage Autophagy: The Role of the PI3K-Akt-mTOR Pathway.

Liu Chunping C Chen Guiling G Chen Yanfen Y Dang Yue Y Nie Guangning G Wu Dinghong D Li Jinhua J Chen Zide Z Yang Hailong H He Dongyue D Li Xiong X Sun Jingbo J Lu Jiahong J Wang Lei L

Frontiers in pharmacology 20210908

Atherosclerosis (AS) is a type of chronic vascular disease, and its etiology is not yet fully understood. AS is characterized by lipid deposition, atherosclerotic plaque formation, vascular stenosis or even complete blockage of the blood vessel wall. Clinical studies have shown that Danlou tablets (DLTs) can improve the heart function, quality of life, and prognosis of patients with coronary heart disease and myocardial infarction. However, its mechanism of action remains unknown. Our study reve ...[more]

PMID: 34566648

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Project description:BackgroundAtherosclerosis is one of the most common cardiovascular disorders. The dysfunction of vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) are 2 key factors in the formation of atherosclerosis. This study aims to find strategies to prevent VSMCs and ECs dysfunction for the treatment of atherosclerosis.MethodsWe investigated the expression patterns of long noncoding RNAs (lncRNAs) in 2 pairs of serum samples from both atherosclerosis patients and healthy volunteers through microarray analysis. Then we selected the most up-regulated lncRNA ENAST00113 (lnc00113) to further verify its roles in atherosclerosis. VSMCs, and human umbilical vein endothelial cells (HUVECs) transfected with small interfering RNA (siRNAs) (si-00113-1, si-00113-1) and a negative control (si-NC) were cultured. MTT assay, Caspase 3 enzyme-linked immunosorbent assay (ELISA) assay, and wound healing assay were performed to evaluate whether lnc00113 had an effect on proliferation, apoptosis, and migration ability. Further, the correlation between lnc00113 and PI3K/Akt/mTOR signaling pathway was explored.ResultsMicroarray results indicated that 243 lncRNAs were up-regulated and 187 lncRNAs were down-regulated. Therefore, we chose the most up-regulated lncRNA ENST (lnc00113) to further explore its roles in atherosclerosis. Real-time polymerase chain reaction (RT-qPCR) results showed that the expression of lnc00113 was highly increased in atherosclerosis patients. In vitro experiment demonstrated that lnc00113 down-regulation significantly suppressed VSMCs and HUVECs proliferation, survival, and migration. Furthermore, we found that the protein expressions of phosphorylated-PI3K (p-PI3K), phosphorylated-Akt (p-Akt), phosphorylated-mTOR (p-mTOR), and bcl-2 in HUVECs cells transfected with si-00113-1 or si-00113-2 were dramatically decreased compared with si-NC-transfected cells and control cells. However, the total- PI3K (t-PI3K), total-Akt (t-Akt), and total-mTOR (t-mTOR) protein expressions were not changed, indicating that lnc00113 could activate PI3K/Akt/mTOR signaling pathway in atherosclerosis.ConclusionsThis finding identified an important role of lnc00113 in VSMCs and HUVECs that promotes cell proliferation, survival, and migration by activating PI3K/Akt/mTOR signaling pathway, which could probably serve as a promising therapeutic target for atherosclerosis.

Dataset Information

Danlou Tablets Inhibit Atherosclerosis in Apolipoprotein E-Deficient Mice by Inducing Macrophage Autophagy: The Role of the PI3K-Akt-mTOR Pathway.

Publications

Danlou Tablets Inhibit Atherosclerosis in Apolipoprotein E-Deficient Mice by Inducing Macrophage Autophagy: The Role of the PI3K-Akt-mTOR Pathway.

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