MicroRNA-19b promotes macrophage cholesterol accumulation and aortic atherosclerosis by targeting ATP-binding cassette transporter A1

Lv, Yun-Cheng; Tang, Yue; Peng, Juan; Zhao, Guo-Jun; Yang, Jing; Yao, Feng; Ouyang, Xin; He, Ping; Xie, Wei; Tan, Yanhong; Zhang, Min; Liu, Dan; Tang, Deng-Pei; Cayabyab, Francisco S.; Zheng, Xi-Long; Zhang, Dawei; Tian, Guo-Ping; Tang, Chao-Ke

doi:10.1016/j.atherosclerosis.2014.07.005

Cited by 106 publications

(59 citation statements)

References 42 publications

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“…In line with a proatherogenic role of miR-19a, the second miR-19 family member miR-19b, which differs only in 1 nucleotide from miR-19a, increases atherosclerosis. 31 In conclusion, we found that endothelial HIF-1α promotes the development of atherosclerosis by mediating the effects of unsaturated LPA on endothelial inflammation and monocyte recruitment through upregulation of miR-19a.…”

Section: Discussionmentioning

confidence: 96%

Endothelial Hypoxia-Inducible Factor-1α Promotes Atherosclerosis and Monocyte Recruitment by Upregulating MicroRNA-19a

et al. 2015

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Chemokines mediate monocyte adhesion to dysfunctional endothelial cells (ECs) and promote arterial inflammation during atherosclerosis. Hypoxia-inducible factor (HIF)-1α is expressed in various cell types of atherosclerotic lesions and is associated with lesional inflammation. However, the impact of endothelial HIF-1α in atherosclerosis is unclear. HIF-1α was detectable in the nucleus of ECs covering murine and human atherosclerotic lesions. To study the role of endothelial HIF-1α in atherosclerosis, deletion of the Hif1 a gene was induced in ECs from apolipoprotein E knockout mice (EC- Hif1a −/− ) by Tamoxifen injection. The formation of atherosclerotic lesions, the lesional macrophage accumulation, and the expression of CXCL1 in ECs were reduced after partial carotid ligation in EC- Hif1a −/− compared with control mice. Moreover, the lesion area and the lesional macrophage accumulation were decreased in the aortas of EC- Hif1a −/− mice compared with control mice during diet-induced atherosclerosis. In vitro, mildly oxidized low-density lipoprotein or lysophosphatidic acid 20:4 increased endothelial CXCL1 expression and monocyte adhesion by inducing HIF-1α expression. Moreover, endothelial Hif1a deficiency resulted in downregulation of miR-19a in atherosclerotic arteries determined by microRNA profiling. In vitro, HIF-1α–induced miR-19a expression mediated the upregulation of CXCL1 in mildly oxidized low-density lipoprotein–stimulated ECs. These results indicate that hyperlipidemia upregulates HIF-1α expression in ECs by mildly oxidized low-density lipoprotein–derived unsaturated lysophosphatidic acid. Endothelial HIF-1α promoted atherosclerosis by triggering miR-19a–mediated CXCL1 expression and monocyte adhesion, indicating that inhibition of the endothelial HIF-1α/miR-19a pathway may be a therapeutic option against atherosclerosis.

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Section: Discussionmentioning

confidence: 96%

Endothelial Hypoxia-Inducible Factor-1α Promotes Atherosclerosis and Monocyte Recruitment by Upregulating MicroRNA-19a

et al. 2015

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“…proliferator-activated receptor γ coactivator 1α (PGC-1α) during the progression of atherosclerosis and that it promotes macrophage cholesterol accumulation, foam cell formation and aortic atherosclerotic development by targeting ATP-binding cassette transporter A1 (ABCA1) [42,43]. In addition, miR-19b has been found to be upregulated in plasma of unstable angina pectoris (UAP) patients, and may play an anti-thrombotic role by targeting tissue factor (TF) [44], which is an essential pro-coagulant protein.…”

Section: The Expression Pattern Of Plasma Ctnimentioning

confidence: 99%

Circulating MiR-19b-3p, MiR-134-5p and MiR-186-5p are Promising Novel Biomarkers for Early Diagnosis of Acute Myocardial Infarction

Wang¹,

Zhao²,

Liu³

et al. 2016

Cell Physiol Biochem

118

103

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Background/Aims: Recent studies have shown that circulating microRNAs (miRNAs) are emerging as promising biomarkers for cardiovascular diseases. This study aimed to determine whether miR-19b-3p, miR-134-5p and miR-186-5p can be used as novel indicators for acute myocardial infarction (AMI). Methods: To investigate the kinetic expression of the three selected miRNAs, we enrolled 18 patients with AMI and 20 matched controls. Plasma samples were collected from each participant, and total RNA was extracted. Quantitative real-time PCR and ELISA assays were used to investigate the expression of circulating miRNAs and cardiac troponin I (cTnI), respectively. Plasma samples from another age- and gender-matched cohort were collected to investigate the impact of medications for AMI on the expression of the selected miRNAs. Results: Levels of plasma miR-19b-3p, miR-134-5p and miR-186-5p were significantly increased in early stage of AMI. Plasma miR-19b-3p and miR-134-5p levels reached peak expression immediately after admission (T0), whereas miR-186-5p achieved peak expression at 4 h after T0. All of these times were earlier than the peak for cTnI (8 h after T0). In addition, all three miRNAs were positively correlated with cTnI. Receiver Operating Characteristic (ROC) analysis indicated that each single miRNA showed considerable diagnostic efficiency for predicting AMI. Furthermore, combining all three miRNAs in a panel increased the efficiency of distinguishing between patients with AMI and controls. Moreover, we found that heparin and medications for AMI did not impact the expression of these circulating miRNAs. Conclusion: Circulating miR-19b-3p, miR-134-5p and miR-186-5p could be considered promising novel diagnostic biomarkers for the early phase of AMI.

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“…Cellular cholesterol levels were analyzed by high performance liquid chromatography (HPLC) as described previously [15,16]. Cells were detached in PBS supplemented with 1% EDTA (T4174; Sigma).…”

Section: Lipid Analysis By High Performance Liquid Chromatography (Hpmentioning

confidence: 99%

Luteolin Attenuates Foam Cell Formation and Apoptosis in Ox-LDL-Stimulated Macrophages by Enhancing Autophagy

Zhang

Wang

et al. 2016

Cell Physiol Biochem

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Background: Our previous studies demonstrated that luteolin, which is rich in flavones, has various biological properties and can exert anti-oxidant, anti-inflammatory and anti-apoptotic activities. However, its effect on ox-LDL-induced macrophage lipid accumulation and apoptosis has not been revealed. Aims: This study aimed to explore the role of luteolin in ox-LDL-induced macrophage-derived foam cell formation and apoptosis and to delineate the underlying mechanism. Methods: Murine RAW264.7 cells were stimulated with oxidized low-density lipoprotein (ox-LDL) (50 µg/ml) for 24 h and then pretreated with 25 µM luteolin for another 24 h. The effects of luteolin on lipid accumulation in RAW264.7 cells induced by ox-LDL were assayed using Oil red O staining and high performance liquid chromatography (HPLC). Apoptosis was confirmed by acridine orange/ethidium bromide (AO/EB) staining, flow cytometric analysis and the TUNEL assay. Immunofluorescence, Western blot and monodansylcadaverine (MDC) staining analyses were then used to further investigate the molecular mechanisms by which luteolin protects macrophages from ox-LDL-induced foam cell formation and apoptosis. 3-Methyladenine (3-MA), an autophagy inhibitor, was used as a positive control. Results: Treatment with 25 µM luteolin not only significantly attenuated ox-LDL-induced macrophage lipid accumulation but also decreased the apoptotic rate of RAW264.7 cells, the number of TUNEL-positive macrophages and the expression of Bax, Bak, cleaved caspase-9 and cleaved caspase-3. In addition, luteolin pretreatment significantly increased autophagosome formation and Beclin-1 activity, thus increasing the ratio of LC3-II/LC3-I. Moreover, these effects were abolished by 3-MA. Conclusions: Taken together, these results highlight that luteolin treatment attenuates foam cell formation and macrophage apoptosis by promoting autophagy and provide new insights into the molecular mechanism of luteolin and its therapeutic potential in the treatment of atherosclerosis.

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MicroRNA-19b promotes macrophage cholesterol accumulation and aortic atherosclerosis by targeting ATP-binding cassette transporter A1

Cited by 106 publications

References 42 publications

Endothelial Hypoxia-Inducible Factor-1α Promotes Atherosclerosis and Monocyte Recruitment by Upregulating MicroRNA-19a

Endothelial Hypoxia-Inducible Factor-1α Promotes Atherosclerosis and Monocyte Recruitment by Upregulating MicroRNA-19a

Circulating MiR-19b-3p, MiR-134-5p and MiR-186-5p are Promising Novel Biomarkers for Early Diagnosis of Acute Myocardial Infarction

Luteolin Attenuates Foam Cell Formation and Apoptosis in Ox-LDL-Stimulated Macrophages by Enhancing Autophagy

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