ASIC1/RIP1 accelerates atherosclerosis via disrupting lipophagy.

Atherosclerosis, a major contributor to cardiovascular disease, remains a significant health concern worldwide. While previous research has shown that acid-sensing ion channel 1 (ASIC1) impedes macrophage cholesterol efflux, its precise role in atherogenesis and the underlying mechanisms have remained elusive. This study aimed to investigate the role of ASIC1 in atherosclerosis and its underlying mechanisms. First, data from a single-cell RNA sequencing (scRNA-seq) database were used to explore the relationships between ASIC1 differential expression and lipophagy in human atherosclerotic lesions. Finally, we validated the role of ASIC1/RIP1 signaling in lipophagy in vivo (human and mice) and in vitro (RAW264.7 and HTP-1 cells). Our results demonstrated a significant increase in ASIC1 protein levels within CD68+ macrophages in both human aortic lesions and AopE Our findings unveil the critical role of macrophage ASIC1 in interacting with RIP1 to inhibit lipophagy, thereby promoting atherogenesis. Targeting ASIC1 represents a promising therapeutic avenue for the treatment of atherosclerosis.

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Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: No conflict of financial or proprietary interest exits in the submission of this manuscript, and this manuscript has not been submitted elsewhere for publication, in whole or in part. All the authors listed have approved the publication of this manuscript.