Inhibition of miR-200b-3p alleviates lipid accumulation and promotes cholesterol efflux by targeting ABCA1 in macrophage-derived foam cells

Abstract

Atherosclerosis (As) is a chronic cardiovascular disease characterized by abnormal of lipid accumulation and cholesterol efflux. The present study aimed to investigate whether the micro-RNA (miR)-200b-3p could exacerbate As by promoting lipid accumulation and inhibiting cholesterol efflux via ATP-binding cassette transporter A1 (ABCA1) in macrophage-derived foam cells. Blood samples from 30 patients with As and 30 healthy people were collected at Quanzhou First Hospital. RAW264.7 cells were used to establish foam cells using oxidized low-density lipoprotein. The expression of miR-200b-3p and ABCA1 was evaluated by reverse transcription quantitative PCR and western blotting. Lipid accumulation was analyzed by Oil Red O staining and cholesterol content was assessed by ELISA. A targeting relationship between miR-200b-3p and ABCA1 was demonstrated by luciferase reporter assays. Compared with healthy volunteers and RAW264.7 cells, the expression level of miR-200b-3p was significantly increased whereas the expression level of ABCA1 was significantly decreased in patients with As and foam cells. Furthermore, miR-200b-3p expression was negatively correlated with ABCA1 expression in the blood of the patients with As. Lipid content was significantly decreased and cholesterol efflux was significantly increased in foam cells transfected with the miR-200b-3p inhibitor compared with inhibitor control cells. In addition, ABCA1 was shown to be targeted by miR-200b-3p. Furthermore, the lipid content in foam cells transfected with the miR-200b-3p inhibitor and small interfering-ABCA1 was significantly increased, while the cholesterol efflux was significantly decreased compared with foam cells transfected with the miR-200b-3p inhibitor. In conclusion, the findings from the present study indicated that inhibition of miR-200b-3p may alleviate lipid accumulation and promote cholesterol efflux by targeting ABCA1 in macrophage-derived foam cells.

Synthetic role of miR‐200b‐3p, ABCD2 score, and carotid ultrasound in the prediction of cerebral infarction in patients with transient ischemic attack

“…According to previous studies, carotid stenosis caused by carotid web lesions was a risk factor for the occurrence of TIA (Hu et al., 2019 ) and changes in miR‐200b‐3p expression were found in degenerative aortic stenosis patient tissues (Shi et al., 2016 ). Meanwhile, another study suggested a link between miR‐200b‐3p and lipid metabolism (Wu et al., 2021 ). Thus, it can be deduced that miR‐200b‐3p might be closely related with carotid stenosis and dyslipidemia.…”

“…Wu et al. ( 2021 ) has reported that the knockdown of miR‐200b‐3p alleviated lipid accumulation and promoted cholesterol efflux, which were two characteristics in the pathogenesis of atherosclerosis, by targeting ABCA 1 . Another study found that miR‐200b‐3p was involved in the regulation of angiogenesis by directly regulating the vascular endothelial growth factor (VEGF) signaling (Choi et al., 2011 ).…”

“…200b-3p were independently associated with CI onset in TIA patients.Second,, ABCD 2 score, and carotid stenosis degree had accuracy in the prediction of CI onset in TIA patients, and the accuracy of the combination of miR-200b-3p, ABCD 2 score, and carotid stenosis degree was best in the prediction of CI onset in TIA patients. The above study has proved that the synthetic role of miR-200b-3p, ABCD 2 score, and carotid stenosis degree might be a good method to screen TIA patients at high risk of CI.The specific mechanism or signaling pathways by which serum miR-200b-3p participated in the progression of TIA has not been explored in depth in our study, which was the limitation of this article as well as the direction of our next research Wu et al (2021). has reported that the knockdown of miR-200b-3p alleviated lipid accumulation and promoted cholesterol efflux, which were two characteristics in the pathogenesis of atherosclerosis, by targeting ABCA 1 .…”

“…MicroRNA‐200b‐3p (miR‐200b‐3p), as one of the highly stable noncoding RNAs, has been implicated in the development and progression of several cerebrovascular‐related diseases (Choi et al., 2011 ; Kim et al., 2016 ; Wu et al., 2021 ). First, in terms of lipid metabolism, Wu et al.…”

“…First, in terms of lipid metabolism, Wu et al. ( 2021 ) unmasked that silencing miR‐200b‐3p could significantly improve lipid accumulation and cholesterol efflux phenomenon in macrophages. Second, in the process of angiogenesis, early studies reported that miR‐200b‐3p regulated the activity of vascular endothelial cells and angiogenesis and other processes via regulating endothelial growth factor signaling pathways (Choi et al., 2011 ).…”