The orphan receptor GPRC5B promotes macrophage infiltration and an inflammatory plaque phenotype in atherosclerosis.

Abstract

BACKGROUND AND AIMS: Atherosclerosis is driven by chronic inflammation of the vascular wall, in which macrophages play a central role. The orphan G protein-coupled receptor GPRC5B is expressed in vascular cells and macrophages and is upregulated during monocyte-to-macrophage differentiation. It has been shown to activate NFκB-dependent inflammatory pathways in adipose tissue and glomeruli. Here, we investigated the impact of GPRC5B on macrophage infiltration and the progression of atherosclerotic plaque development in vivo. METHODS: Bone marrow from heterozygous GPRC5B-transgenic C57BL/6 mice and wild-type controls was transplanted into lethally irradiated LDL receptor-deficient mice. Animals were fed a Western-type diet for 16 weeks, after which atherosclerotic lesions in the aortic sinus were analyzed. RESULTS: Mice receiving GPRC5B-transgenic bone marrow showed no significant differences in serum lipids or cardiac mass indices. However, they exhibited significantly increased macrophage infiltration within atherosclerotic plaques and a non-significant trend toward larger and more complex lesions. CONCLUSIONS: GPRC5B overexpression in bone marrow-derived monocyte/macrophage lineage cells promotes a more inflammatory plaque phenotype, characterized by enhanced macrophage infiltration. These findings highlight GPRC5B as a potential modulator of plaque progression and suggest it may represent a novel therapeutic target in vascular inflammation and atherosclerosis.