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. To investigate the role of brain soluble acid protein 1 positive (BASP1⁺) monocyte subset in promoting AAD development as well as the underlying mechanism. 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. "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. 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.

Aortic dissection (AD) is a cardiovascular disease that seriously endangers the lives of patients. The mortality rate of this disease is high, and the incidence is increasing annually, but the pathogenesis of AD is complicated. In recent years, an increasing number of studies have shown that immune cell infiltration in the media and adventitia of the aorta is a novel hallmark of AD. These cells contribute to changes in the immune microenvironment, which can affect their own metabolism and that of parenchymal cells in the aortic wall, which are essential factors that induce degeneration and remodeling of the vascular wall and play important roles in the formation and development of AD. Accordingly, this review focuses on the independent and interactive roles of immunity and metabolism in AD to provide further insights into the pathogenesis, novel ideas for diagnosis and new strategies for treatment or early prevention of AD.