Rosmarinic Acid Increases Macrophage Cholesterol Efflux through Regulation of ABCA1 and ABCG1 in Different Mechanisms
Lipid dysregulation in diabetes mellitus escalates endothelial dysfunction, the initial event in the development and progression of diabetic atherosclerosis. In addition, lipid-laden macrophage accumulation in the arterial wall plays a significant role in the pathology of diabetes-associated atheros...
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MDPI AG
2021-08-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/16/8791 |
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| author | Jean-Baptiste Nyandwi Young Shin Ko Hana Jin Seung Pil Yun Sang Won Park Hye Jung Kim |
| author_facet | Jean-Baptiste Nyandwi Young Shin Ko Hana Jin Seung Pil Yun Sang Won Park Hye Jung Kim |
| author_sort | Jean-Baptiste Nyandwi |
| collection | DOAJ |
| description | Lipid dysregulation in diabetes mellitus escalates endothelial dysfunction, the initial event in the development and progression of diabetic atherosclerosis. In addition, lipid-laden macrophage accumulation in the arterial wall plays a significant role in the pathology of diabetes-associated atherosclerosis. Therefore, inhibition of endothelial dysfunction and enhancement of macrophage cholesterol efflux is the important antiatherogenic mechanism. Rosmarinic acid (RA) possesses beneficial properties, including its anti-inflammatory, antioxidant, antidiabetic and cardioprotective effects. We previously reported that RA effectively inhibits diabetic endothelial dysfunction by inhibiting inflammasome activation in endothelial cells. However, its effect on cholesterol efflux remains unknown. Therefore, in this study, we aimed to assess the effect of RA on cholesterol efflux and its underlying mechanisms in macrophages. RA effectively reduced oxLDL-induced cholesterol contents under high glucose (HG) conditions in macrophages. RA enhanced ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) expression, promoting macrophage cholesterol efflux. Mechanistically, RA differentially regulated ABCA1 expression through JAK2/STAT3, JNK and PKC-p38 and ABCG1 expression through JAK2/STAT3, JNK and PKC-ERK1/2/p38 in macrophages. Moreover, RA primarily stabilized ABCA1 rather than ABCG1 protein levels by impairing protein degradation. These findings suggest RA as a candidate therapeutic to prevent atherosclerotic cardiovascular disease complications related to diabetes by regulating cholesterol efflux in macrophages. |
| first_indexed | 2024-03-10T08:44:41Z |
| format | Article |
| id | doaj.art-46ab45775e9045c38d504c3f952f3b9b |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T08:44:41Z |
| publishDate | 2021-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-46ab45775e9045c38d504c3f952f3b9b2023-11-22T08:00:41ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-08-012216879110.3390/ijms22168791Rosmarinic Acid Increases Macrophage Cholesterol Efflux through Regulation of ABCA1 and ABCG1 in Different MechanismsJean-Baptiste Nyandwi0Young Shin Ko1Hana Jin2Seung Pil Yun3Sang Won Park4Hye Jung Kim5Department of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaDepartment of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaDepartment of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaDepartment of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaDepartment of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaDepartment of Pharmacology, Institute of Health Sciences, College of Medicine, Gyeongsang National University, Jinju 52727, KoreaLipid dysregulation in diabetes mellitus escalates endothelial dysfunction, the initial event in the development and progression of diabetic atherosclerosis. In addition, lipid-laden macrophage accumulation in the arterial wall plays a significant role in the pathology of diabetes-associated atherosclerosis. Therefore, inhibition of endothelial dysfunction and enhancement of macrophage cholesterol efflux is the important antiatherogenic mechanism. Rosmarinic acid (RA) possesses beneficial properties, including its anti-inflammatory, antioxidant, antidiabetic and cardioprotective effects. We previously reported that RA effectively inhibits diabetic endothelial dysfunction by inhibiting inflammasome activation in endothelial cells. However, its effect on cholesterol efflux remains unknown. Therefore, in this study, we aimed to assess the effect of RA on cholesterol efflux and its underlying mechanisms in macrophages. RA effectively reduced oxLDL-induced cholesterol contents under high glucose (HG) conditions in macrophages. RA enhanced ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) expression, promoting macrophage cholesterol efflux. Mechanistically, RA differentially regulated ABCA1 expression through JAK2/STAT3, JNK and PKC-p38 and ABCG1 expression through JAK2/STAT3, JNK and PKC-ERK1/2/p38 in macrophages. Moreover, RA primarily stabilized ABCA1 rather than ABCG1 protein levels by impairing protein degradation. These findings suggest RA as a candidate therapeutic to prevent atherosclerotic cardiovascular disease complications related to diabetes by regulating cholesterol efflux in macrophages.https://www.mdpi.com/1422-0067/22/16/8791ABCA1ABCG1cholesterol effluxdiabetic atherosclerosismacrophagesrosmarinic acid |
| spellingShingle | Jean-Baptiste Nyandwi Young Shin Ko Hana Jin Seung Pil Yun Sang Won Park Hye Jung Kim Rosmarinic Acid Increases Macrophage Cholesterol Efflux through Regulation of ABCA1 and ABCG1 in Different Mechanisms International Journal of Molecular Sciences ABCA1 ABCG1 cholesterol efflux diabetic atherosclerosis macrophages rosmarinic acid |
| title | Rosmarinic Acid Increases Macrophage Cholesterol Efflux through Regulation of ABCA1 and ABCG1 in Different Mechanisms |
| title_full | Rosmarinic Acid Increases Macrophage Cholesterol Efflux through Regulation of ABCA1 and ABCG1 in Different Mechanisms |
| title_fullStr | Rosmarinic Acid Increases Macrophage Cholesterol Efflux through Regulation of ABCA1 and ABCG1 in Different Mechanisms |
| title_full_unstemmed | Rosmarinic Acid Increases Macrophage Cholesterol Efflux through Regulation of ABCA1 and ABCG1 in Different Mechanisms |
| title_short | Rosmarinic Acid Increases Macrophage Cholesterol Efflux through Regulation of ABCA1 and ABCG1 in Different Mechanisms |
| title_sort | rosmarinic acid increases macrophage cholesterol efflux through regulation of abca1 and abcg1 in different mechanisms |
| topic | ABCA1 ABCG1 cholesterol efflux diabetic atherosclerosis macrophages rosmarinic acid |
| url | https://www.mdpi.com/1422-0067/22/16/8791 |
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