# Increased atherosclerosis and expression of inflammarafts in macrophage foam cells in AIBP-deficient mice

## TL;DR

AIBP deficiency in mice leads to more severe atherosclerosis and increased inflammation in macrophage foam cells.

## Contribution

This study reveals that AIBP deficiency alters foam cell characteristics and promotes advanced atherosclerosis.

## Key findings

- AIBP-deficient mice had more lipid-laden foam cells and larger atherosclerotic lesions.
- AIBP deficiency increased inflammaraft markers like TLR4 dimers in foam cells.
- AIBP-deficient macrophages showed higher expression of inflammation-related genes.

## Abstract

Atherosclerotic lesions comprise different populations of macrophages, including lipid-laden macrophage foam cells and non-foamy, inflammatory macrophages, which play distinct roles in disease progression. Non-foamy macrophages express higher levels of inflammarafts – enlarged, cholesterol-rich lipid rafts hosting assemblies of inflammatory receptors – compared to foam cells in atherosclerotic lesions of Ldlr−/− mice. Apolipoprotein A-I binding protein (AIBP) has been shown to control lipid raft dynamics. This study investigated the effect of systemic AIBP deficiency on inflammaraft expression in foam cells and non-foamy macrophages in atherosclerotic lesions of hypercholesterolemic mice. A larger number of foam cells, with increased neutral lipid accumulation, populated atherosclerotic lesions in Apoa1bp−/−Ldlr−/− mice compared to Ldlr−/− mice. Importantly, AIBP-deficient foam cells expressed higher levels of TLR4 dimers and lipid rafts (markers of inflammarafts) than control mice, accompanied by larger atherosclerotic lesions and larger necrotic cores compared to Ldlr−/− mice. In a model of foam cells, Apoa1bp−/− bone marrow-derived macrophages incubated with oxidized LDL had increased expression of inflammation and atherosclerosis related genes. These results indicate that AIBP deficiency results in a phenotype shift in foam cells, characterized by increased lipid accumulation and increased expression of inflammarafts, and it correlates with the development of advanced atherosclerotic plaques.

The online version contains supplementary material available at 10.1038/s41598-026-39113-2.