Serum amyloid A3 deficiency modulates aortic immune composition and attenuates murine atherosclerosis progression
Year: 2024
Type: preprint
Abstract: Atherosclerosis is a growing concern in developed nations, necessitating the identification of therapeutic targets for advancing personalized medicine. Serum amyloid A3 ( Saa3 ) has been linked to accelerated plaque progression by affecting cholesterol metabolism and modulation of inflammation. We hypothesize that knocking out Saa3 ( Saa3 −/− ) could mitigate plaque development by regulating aortic immune cell compositions during atherosclerosis progression. Using a murine model, we induced atherosclerosis via a gain-of-function mutant PCSK9-encoding adeno-associated viral vector (AAVmPCSK9) in female wild-type (WT) and Saa3 −/− mice. Saa3 −/− mice developed smaller plaques than WT mice, and single-cell RNA sequencing revealed significant differences in aortic immune cell populations, particularly among aortic macrophages. Aortic macrophages in atherosclerotic Saa3 −/− mice represent an anti-inflammatory and tissue-repairing phenotype and the Trem2 hi macrophages, characterized by high Gpnmb , Lpl , and Spp1 expressions, predominated over the typical foamy macrophages in Saa3 −/− compared to WT mice. Notably, SAA3 regulates cholesterol metabolism and inflammatory responses in foamy macrophages. Our study highlights Saa3 as a key modulator of aortic immune cells that impact atherosclerosis progression.
Authors: Tzu-Yin Chou, Yu-Zhen Ye, Chia-Jung Lien, Jui-Chun Wang, Chen-Hsuan Yang, Yen-Ting Chen, Pei-An Chao, Jian-Da Lin
Institution: National Taiwan University
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W4400607828