Dataset Information

Astaxanthin Alleviates Foam Cell Formation and Promotes Cholesterol Efflux in Ox-LDL-Induced RAW264.7 Cells via CircTPP2/miR-3073b-5p/ABCA1 Pathway.

ABSTRACT: Atherosclerosis (AS) is a common cardiovascular disease and remains the leading cause of death in the world. It is generally believed that the deposition of foam cells in the arterial wall is the main cause of AS. Moreover, promoting cholesterol efflux and enhancing the ability of reverse cholesterol transport (RCT) can effectively inhibit the formation of foam cells, thereby preventing the occurrence and development of AS. Astaxanthin, with a powerful antioxidant ability, has a potential role in the prevention of atherosclerosis, but how it works in preventing atherosclerosis remains unknown. Here, our experimental results suggest that astaxanthin can upregulate the expression of circular RNA tripeptidyl-peptidase II (circTPP2) and eventually promote cholesterol efflux by modulating ATP-binding cassette subfamily A member 1 (ABCA1). The expression of ABCA1 was significantly suppressed after knocking down circTPP2 in macrophage-derived foam cells. In addition, the experimental results showed that circTPP2 could downregulate the expression of microRNA-3073b-5p (miR-3073b-5p), and ABCA1 was identified as the target gene of miR-3073b-5p. In conclusion, the circTPP2/miR-3073b-5p/ABCA1 axis may be the specific mechanism of astaxanthin promoting cholesterol efflux.

SUBMITTER: Zhang Z

PROVIDER: S-EPMC9961242 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Astaxanthin Alleviates Foam Cell Formation and Promotes Cholesterol Efflux in Ox-LDL-Induced RAW264.7 Cells via CircTPP2/miR-3073b-5p/ABCA1 Pathway.

Zhang Zhexiao Z Qiu Yunmei Y Li Wanzhi W Tang Anyang A Huang Hang H Yao Wanyi W Li Huawen H Zou Tangbin T

Molecules (Basel, Switzerland) 20230210 4

Atherosclerosis (AS) is a common cardiovascular disease and remains the leading cause of death in the world. It is generally believed that the deposition of foam cells in the arterial wall is the main cause of AS. Moreover, promoting cholesterol efflux and enhancing the ability of reverse cholesterol transport (RCT) can effectively inhibit the formation of foam cells, thereby preventing the occurrence and development of AS. Astaxanthin, with a powerful antioxidant ability, has a potential role i ...[more]

PMID: 36838686

Similar Datasets

Project description:Introduction: Atherosclerosis is the main cause of many cardiovascular diseases and contributes to morbidity and mortality worldwide. The formation of macrophage-derived foam cells plays a critical role in the early stage of atherosclerosis pathogenesis. Diterpenoids found in the flowers of Callicarpa rubella Lindl., a traditional Chinese medicine, have been reported to have anti-inflammatory activity. However, little is known about the effects of these diterpenoids on macrophage foam cell formation. Methods: A macrophage-derived foam cell formation model was established by treating RAW264.7 cells with oxidized low-density lipoprotein (ox-LDL) for 24 h. Oil red O staining were used to detect the intracellular lipids. The cholesterol efflux capacity was assayed by labeling cells with 22-NBD-cholesterol. Western blots and real-time PCRs were performed to quantify protein and mRNA expressions. Results: Two diterpenoid molecules, 14α-hydroxyisopimaric acid (C069002) and isopimaric acid (C069004), extracted from the flowers of Callicarpa rubella Lindl., significantly attenuated ox-LDL-induced foam cell formation in RAW264.7 macrophages. Further investigation showed that these two diterpenoids could promote cholesterol efflux from RAW264.7 macrophages to apolipoprotein A-I or high-density lipoproteins, which was associated with upregulated expression of ATP-binding cassette A1/G1 (ABCA1/G1), liver X receptor-α (LXRα), and peroxisome proliferator-activated receptor-γ (PPARγ). Unexpectedly, the diterpenoids C069002 and C069004 failed to enhance the mRNA transcription of the ABCG1 gene in macrophage-derived foam cells induced by ox-LDL. To evaluate the effects of diterpenoids on macrophage foam cell formation and determine the underlying mechanism, two drugs (lovastatin and rosiglitazone) were used as positive controls. Although both drugs could reduce macrophage foam cell formation and promote cholesterol efflux, they each had distinctive abilities to modulate the expression of cholesterol efflux-related genes. In contrast to lovastatin, rosiglitazone showed a similar influence on the expression of cholesterol efflux-related genes (including ABCA1, LXRα, and PPARγ) as the diterpenoids regardless of the presence or absence of ox-LDL, implying a similar mechanism by which they may exert atheroprotective effects. Conclusion: Our research indicates that diterpenoids effectively inhibit ox-LDL-induced macrophage foam cell formation by promoting cholesterol efflux from macrophages via the PPARγ-LXRα-ABCA1 pathway. Further investigation of diterpenoids as potential drugs for the treatment of atherosclerosis is warranted.

Project description:Atherosclerosis (AS), a major cause of cardiovascular disease, has developed into a serious challenge to the health system. The long non‑coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) is associated with the pathogenesis of AS. However, whether MALAT1 can affect cholesterol accumulation in macrophages during AS progression, and the potential molecular mechanism involved in this progression have not been elucidated. In the present study, the mRNA expression level of MALAT1 was measured using reverse transcription‑quantitative PCR (RT‑qPCR) and the protein expression level was detected via western blot analysis. Oil Red O staining was used for detecting lipid accumulation in macrophages. Bioinformatics, dual‑luciferase reporter and RT‑qPCR assays were used to investigate the relationship between MALAT1 and the microRNA (miR)‑17‑5p/ATP‑binding cassette transporter A1 (ABCA1) axis. The present results suggested that the MALAT1 expression level was significantly decreased in patients with AS and in oxidized low‑density lipoprotein (ox‑LDL)‑stimulated macrophages. Knockdown of MALAT1 increased ox‑LDL uptake, lipid accumulation and the total cholesterol (T‑CHO) level in ox‑LDL‑induced macrophages. In addition, MALAT1 inhibition significantly decreased the mRNA and protein expression levels of scavenger receptor (SR) class B member 1, apolipoprotein E (ApoE) and ABCA1. However, MALAT1 increased the expression level of SR class A. Subsequently, the present study investigated whether MALAT1 could target miR‑17‑5p to regulate the expression level of ABCA1, which is involved in cholesterol efflux from macrophages. The present results suggested that inhibition of miR‑17‑5p reversed the effects of MALAT1 knockdown on T‑CHO content, and protein expression levels of ApoE and ABCA1 in ox‑LDL‑stimulated macrophages. In summary, knockdown of MALAT1 may promote cholesterol accumulation by regulating the miR‑17‑5p/ABCA1 axis in ox‑LDL‑induced THP‑1 macrophages.

Dataset Information

Astaxanthin Alleviates Foam Cell Formation and Promotes Cholesterol Efflux in Ox-LDL-Induced RAW264.7 Cells via CircTPP2/miR-3073b-5p/ABCA1 Pathway.

Publications

Astaxanthin Alleviates Foam Cell Formation and Promotes Cholesterol Efflux in Ox-LDL-Induced RAW264.7 Cells via CircTPP2/miR-3073b-5p/ABCA1 Pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets