Resolvin T4 enhances macrophage cholesterol efflux to reduce vascular disease.
Nat Commun
; 15(1): 975, 2024 Feb 05.
Article
in En
| MEDLINE
| ID: mdl-38316794
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Arthritis
/
Atherosclerosis
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Nat Commun
Journal subject:
BIOLOGIA
/
CIENCIA
Year:
2024
Document type:
Article
Country of publication: