神戸大学医学部医学研究科内科学講座循環器内科学分野Division of Cardiovascular Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine― 143 ―Backgrounds: Degenerative aortic valve stenosis (AS) is the age-related cardiovascular disease based on atherosclerosis. The mechanisms leading to aortic valve calcification and its tight association with immune systems remain largely unknown. Therefore, we aimed to identify therapeutic targets of AS by comparing an immune cell landscape between AS and aortic valve regurgitation (AR) samples at a single cell level.Methods: We obtained aortic valve samples from eight AS patients and three AR patients who were candidates for surgical aortic valve replacement. Live CD45 positive immune cells were sorted from aortic valve samples and applied to the 10X platform for single-cell RNAseq analysis. Results: We detected three major immune cell clusters in aortic valves: T cells, myeloid cells, and B cells. In myeloid cells, LYVE-1+ resident macrophages decreased, while classical monocytes increased in AS, compared with AR. In T cells, NK cells were only detected in AS. Histological analysis by phenocycler system revealed inflammatory macrophages and neutrophils are accumulated around calcified regions in AS, while resident macrophages were uniformly distributed in AR.Conclusions: For the first time, we revealed the characteristic immune cell landscape of AS at a single cell level. Maintenance of resident macrophages, regulation of monocyte influx, and suppression of NK cells could be therapeutic targets to treat AS.Abstractはじめに大動脈弁狭窄症は大動脈弁が狭小化することによって左室から上行大動脈への血流が妨げられる病Single cell RNA seq reveals aortic valve stenosis specific シングルセル解析で明らかにする大動脈弁狭窄症特異的マクロファージmacrophages江本 拓央Takuo Emoto
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