Journal of advanced research · 2025
From inflammation to remodelling: A novel BASP1+ monocyte subset as a catalyst for acute aortic dissection.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
He Wenhui, Yu Sanjiu, Li Jun, Li Siyu, Chen Zongtao, Zhang Jingyu, Liu Yangwuyue, Zhou Mi, Yang Teng, Cheng Wei, Dai Shuang-Shuang
Аннотация
INTRODUCTION: Monocytes comprise heterogeneous cell populations. However, beyond traditionally considered as precursors of tissue macrophages, heterogeneity and detailed effects of monocytes in acute aortic dissection (AAD) are largely unknown.
OBJECTIVES: To investigate the role of brain soluble acid protein 1 positive (BASP1+) monocyte subset in promoting AAD development as well as the underlying mechanism.
METHODS: Monocyte/macrophage heterogeneity in both human peripheral blood and aortic tissues were assayed by scRNA-seq. Monocyte trafficking and lineage tracing were detected by immunofluorescence and using BASP1-CreER/Lyz2-DreER-tdT reporter mice with AAD. The effects and underlying mechanism were investigated by laser speckle image, ultrasound imaging, Co-IP, ChIP-sequencing. Conditional knockout of BASP1 on monocyte and BASP1 siRNA were used to observe BASP1+ monocyte subset-targeted AAD intervention.
RESULTS: "PIP2-SP1-ACTN1/VAV3" and "ITGB1-Rac1-GSN" signalling mediated BASP1+ monocyte subset as the first line immune cells infiltrating aortic tissues in AAD induction and partial of them transformed to BASP1+ macrophages to amplify the inflammation. Meanwhile, BASP1+ monocyte subset induced an inflammatory phenotype vascular smooth muscle cell (VSMC) subset and a ROS-enriched endothelial cell (EC) subset accompanied with promoting the apoptosis of normal VSMC and EC, contributing to vascular remodelling and dampening the myo-endothelial gap junction. Selective deletion of BASP1+ monocyte subset and interference with BASP1 expression in monocytes both inhibited the development of AAD in mice.
CONCLUSION: Interpretation BASP1+ monocyte subset and its regulatory network provides deep insight into AAD pathogenesis and a novel potential target for early intervention in AAD formation.
OBJECTIVES: To investigate the role of brain soluble acid protein 1 positive (BASP1+) monocyte subset in promoting AAD development as well as the underlying mechanism.
METHODS: Monocyte/macrophage heterogeneity in both human peripheral blood and aortic tissues were assayed by scRNA-seq. Monocyte trafficking and lineage tracing were detected by immunofluorescence and using BASP1-CreER/Lyz2-DreER-tdT reporter mice with AAD. The effects and underlying mechanism were investigated by laser speckle image, ultrasound imaging, Co-IP, ChIP-sequencing. Conditional knockout of BASP1 on monocyte and BASP1 siRNA were used to observe BASP1+ monocyte subset-targeted AAD intervention.
RESULTS: "PIP2-SP1-ACTN1/VAV3" and "ITGB1-Rac1-GSN" signalling mediated BASP1+ monocyte subset as the first line immune cells infiltrating aortic tissues in AAD induction and partial of them transformed to BASP1+ macrophages to amplify the inflammation. Meanwhile, BASP1+ monocyte subset induced an inflammatory phenotype vascular smooth muscle cell (VSMC) subset and a ROS-enriched endothelial cell (EC) subset accompanied with promoting the apoptosis of normal VSMC and EC, contributing to vascular remodelling and dampening the myo-endothelial gap junction. Selective deletion of BASP1+ monocyte subset and interference with BASP1 expression in monocytes both inhibited the development of AAD in mice.
CONCLUSION: Interpretation BASP1+ monocyte subset and its regulatory network provides deep insight into AAD pathogenesis and a novel potential target for early intervention in AAD formation.