Key result
Resolvin D2 limits cardiac remodeling and improves function in murine heart failure via GPR18-mediated macrophage modulation.
Why the study?
The role of Resolvin D2 in the pathogenesis of heart failure and its potential protective effects via GPR18 were unclear.
Does Resolvin D2 treatment improve cardiac remodeling and function in pressure overload-induced heart failure mice?
Does Resolvin D2 treatment improve cardiac remodeling and function in pressure overload-induced heart failure mice?
The RvD2/GPR18 axis ameliorates pressure overload-induced heart failure in mice by inhibiting pro-inflammatory macrophage polarization via STAT1 and NF-κB p65 pathways.
Accumulating evidence has revealed that chronic unresolved inflammation can cause significant tissue damage and can be a key mediator of advanced heart failure (HF). Resolvin (Rv) D2, a member of specialized pro-resolving lipid mediators (SPMs), plays a protective role in various diseases by facilitating resolution. However, whether RvD2 participates in the pathogenesis of HF is still unclear. Our study demonstrated that RvD2 treatment mitigated cardiac remodeling and improved cardiac function in HF mice induced by pressure overload. The absence of G protein-coupled receptor 18 (GPR18), an endogenous receptor for RvD2, abolished the beneficial effects of RvD2 on HF. Additionally, RvD2 inhibited inflammatory responses and Ly6C high macrophage polarization during both early and late inflammatory stages involved in HF. Further investigation revealed that bone marrow transplantation from G pr 18 deficient mice into WT mice blocked the protective effects of RvD2 in HF mice. Moreover, G pr18 deficiency impeded RvD2's capacity to downregulate inflammatory responses and Ly6C high macrophage polarization. Consistent with experiments in vivo, RvD2 treatment in bone marrow-derived macrophages (BMDMs) reduced inflammatory responses through its receptor GPR18. Mechanistically, RvD2 suppressed the phosphorylation of STAT1 and NF-κB p65, and the effects of RvD2 were reversed by the application of STAT1 or NF-κB p65 agonists in BMDMs . In conclusion, RvD2/GPR18 axis improved cardiac remodeling and function in pressure overload-induced HF mice by modulating macrophage phenotype via STAT1 and NF-κB p65 pathways. Our findings underscore the anti-inflammatory potential of RvD2/GPR18 axis, suggesting that RvD2/GPR18 axis may be a potential strategy for the treatment of HF.
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Zhao et al. (2024) studied Heart failure. Resolvin D2 (RvD2) was evaluated on Cardiac remodeling and function. Resolvin D2 treatment mitigated cardiac remodeling and improved cardiac function in pressure overload-induced heart failure mice by modulating macrophage phenotype via the GPR18 receptor.
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