Increased expression of Cd74 and MHC II genes by aortic macrophages links atherosclerosis with aging in mice

Abstract

Atherosclerosis is a chronic inflammatory condition of the arteries leading to myocardial infarction, ischemic stroke and peripheral arterial diseases. Atherosclerotic plaques, which obstruct blood flow contain functionally diverse macrophage populations including pro-atherogenic and atheroprotective subsets. Aging is a major risk factor of atherosclerosis, but the mechanism underlying aging associated risk of atherosclerosis is unclear. Here, using integrated single-cell RNA sequencing data analysis, we demonstrate that specific monocyte and macrophage subsets are enriched in atherosclerotic plaques and the aging aorta of mice. We also show that Cd74 and MHCII genes such as H2-Aa, H2-Ab1, H2-Eb1, and H2-DMb1 are consistently upregulated in the monocytes and macrophages from atherosclerotic plaques, the aging aorta, and the aging bone marrow of mice. Our experimental data also show increased expression of CD74 surface protein by aortic macrophages and bone marrow monocytes from aged mice. In addition, we show increased CD74 expression by RAW264.7 mouse macrophages and THP1 human monocytes following ox-LDL stimulation in vitro. Finally, we demonstrate that monocytes from aged mice adhere more to aortic endothelial cells in co-cultures. Thus, increased monocyte adhesion to endothelial cells may explain the enhanced proportion of specific monocyte and macrophage subsets in the aging aorta, inducing a pre-atherosclerotic condition.