Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease
Abstract While cardiovascular disease (CVD) is one of the major co-morbidities in patients with rheumatoid arthritis (RA), the mechanism(s) that contribute to CVD in patients with RA remain to be fully elucidated. Herein, we observe that plasma concentrations of 13-series resolvin (RvT)4 negatively...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-02-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-44868-1 |
| _version_ | 1827326777924517888 |
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| author | Mary E. Walker Roberta De Matteis Mauro Perretti Jesmond Dalli |
| author_facet | Mary E. Walker Roberta De Matteis Mauro Perretti Jesmond Dalli |
| author_sort | Mary E. Walker |
| collection | DOAJ |
| description | Abstract While cardiovascular disease (CVD) is one of the major co-morbidities in patients with rheumatoid arthritis (RA), the mechanism(s) that contribute to CVD in patients with RA remain to be fully elucidated. Herein, we observe that plasma concentrations of 13-series resolvin (RvT)4 negatively correlate with vascular lipid load in mouse inflammatory arthritis. Administration of RvT4 to male arthritic mice fed an atherogenic diet significantly reduces atherosclerosis. Assessment of the mechanisms elicited by this mediator demonstrates that RvT4 activates cholesterol efflux in lipid laden macrophages via a Scavenger Receptor class B type 1 (SR-BI)-Neutral Cholesterol Ester Hydrolase-dependent pathway. This leads to the reprogramming of lipid laden macrophages yielding tissue protection. Pharmacological inhibition or knockdown of macrophage SR-BI reverses the vasculo-protective activities of RvT4 in vitro and in male mice in vivo. Together these findings elucidate a RvT4-SR-BI centered mechanism that orchestrates macrophage responses to limit atherosclerosis during inflammatory arthritis. |
| first_indexed | 2024-03-07T14:50:25Z |
| format | Article |
| id | doaj.art-47d7fa7f39ad4526836cf837c92c376e |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-07T14:50:25Z |
| publishDate | 2024-02-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-47d7fa7f39ad4526836cf837c92c376e2024-03-05T19:42:24ZengNature PortfolioNature Communications2041-17232024-02-0115111610.1038/s41467-024-44868-1Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular diseaseMary E. Walker0Roberta De Matteis1Mauro Perretti2Jesmond Dalli3William Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of LondonWilliam Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of LondonWilliam Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of LondonWilliam Harvey Research Institute, Faculty of Medicine and Dentistry, Queen Mary University of LondonAbstract While cardiovascular disease (CVD) is one of the major co-morbidities in patients with rheumatoid arthritis (RA), the mechanism(s) that contribute to CVD in patients with RA remain to be fully elucidated. Herein, we observe that plasma concentrations of 13-series resolvin (RvT)4 negatively correlate with vascular lipid load in mouse inflammatory arthritis. Administration of RvT4 to male arthritic mice fed an atherogenic diet significantly reduces atherosclerosis. Assessment of the mechanisms elicited by this mediator demonstrates that RvT4 activates cholesterol efflux in lipid laden macrophages via a Scavenger Receptor class B type 1 (SR-BI)-Neutral Cholesterol Ester Hydrolase-dependent pathway. This leads to the reprogramming of lipid laden macrophages yielding tissue protection. Pharmacological inhibition or knockdown of macrophage SR-BI reverses the vasculo-protective activities of RvT4 in vitro and in male mice in vivo. Together these findings elucidate a RvT4-SR-BI centered mechanism that orchestrates macrophage responses to limit atherosclerosis during inflammatory arthritis.https://doi.org/10.1038/s41467-024-44868-1 |
| spellingShingle | Mary E. Walker Roberta De Matteis Mauro Perretti Jesmond Dalli Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease Nature Communications |
| title | Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease |
| title_full | Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease |
| title_fullStr | Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease |
| title_full_unstemmed | Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease |
| title_short | Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease |
| title_sort | resolvin t4 enhances macrophage cholesterol efflux to reduce vascular disease |
| url | https://doi.org/10.1038/s41467-024-44868-1 |
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