Unraveling the immunological roles of Serum Amyloid A3 in aortic arches during atherosclerosis progression

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B927
Abstract ID: 4837

Presenting Author:
Tzu-Yin Chou , Research Assistant at Natl. Taiwan Univ.

Abstract:

Atherosclerosis is a growing concern in developed nations. Identifying therapeutic targets is imperative for advancing personalized medicine. Serum amyloid A3 (Saa3), a member of the serum amyloid A protein family, has been linked to accelerated plaque progression through changes in cholesterol metabolism and inflammation modulation. While Saa3 is a pseudogene in humans, its study in mouse models provides insight into atherosclerosis regulation. Here, we hypothesize that Saa3 knockout (Saa3^-/-) could mitigate plaque development, aiming to elucidate the underlying mechanisms. Murine atherosclerosis was induced by the injection of a gain-of-function mutant PCSK9–encoding adeno-associated viral vector. Single-cell RNA sequencing was used to scrutinize the cellular composition within the aortic arch during progressive plaque development. Results showed smaller plaques in Saa3^-/- mice compared to wild-type mice, with significant differences in immune cell populations, particularly macrophages. In Saa3^-/- mice, there was a prominent presence of macrophages characterized by high expressions of Gpnmb, Lpl, and Spp1, associated with the atheroprotective growth differentiation factors pathway, dominated over the usual resident foamy macrophages observed in the WT counterparts. Our study underscores that the absence of Saa3 may reprogram macrophages towards a tissue-repairing phenotype, thus reducing plaque size and offering new atherosclerosis treatment avenues.