Proresolving receptor tames inflammation in atherosclerosis
Hebe Agustina Mena, Matthew Spite
Hebe Agustina Mena, Matthew Spite
Published December 15, 2021
Citation Information: J Clin Invest. 2021;131(24):e155240. https://doi.org/10.1172/JCI155240.
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Proresolving receptor tames inflammation in atherosclerosis

Abstract

Nonresolving inflammation contributes to the progression of atherosclerosis, a chronic disease characterized by the accumulation of lipid-rich arterial plaques infiltrated with immune cells. In this issue of the JCI, Arnardottir and Thul et al. report that GPR32, a receptor for proresolving lipid mediators including resolvin D1, was decreased in human atherosclerotic lesions and that overexpression of this human receptor in mice reduced lesion area and necrosis of atherosclerotic plaques. Mechanistically, GPR32 signaling blunted the production of proinflammatory cytokines, enhanced macrophage phagocytosis, and reduced leukocyte accumulation. These results suggest that therapeutic targeting of GPR32 could be an approach to resolving chronic inflammation in atherosclerosis.

Authors

Hebe Agustina Mena, Matthew Spite

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Figure 1

The role of human GPR32 in atherosclerosis.

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The role of human GPR32 in atherosclerosis. Tg overexpression of hGPR32 ...
Tg overexpression of hGPR32 on an Apoe- and Fpr2-deficient background reduces atherosclerotic lesion area and necrotic cores as compared with that of non-Tg Fpr2–/–×Apoe–/– mice. Lesions of hGPR32 Tg mice are characterized by a lower number of monocytes and neutrophils, reduced macrophages, and decreased levels of the proinflammatory cytokine TNF-α. Of note, overexpression of hGPR32 also increases macrophage efferocytosis in peritonitis, and RvD1 enhances macrophage phagocytosis and lowers the uptake of oxidized LDL by macrophages in vitro in an hGPR32-dependent manner. These results suggests that GPR32 has multiple proresolving and atheroprotective roles. Similarly, RvD1 binds GPR32, enhances phagocytosis, and lowers the uptake of oxidized LDL.