The Role of CDCP1 in Carotid Artery Stenosis: Implications for Mitochondrial Autophagy and Therapeutic Potential of 8-isopentenylnaringenin

Carotid artery stenosis (CAS) is a major cause of cardiovascular diseases, such as myocardial infarction and stroke. Mitochondrial dysfunction can trigger the onset of these conditions. CUB Domain Containing Protein 1 (CDCP1) is a transmembrane protein that has been demonstrated to contribute to various tumors and myocardial infarction; however, its role in carotid artery stenosis has not yet been reported. In this study, we investigated how CDCP1 affects cellular activity by regulating mitochondrial autophagy, and we propose that 8-isopentenylnaringenin (8-PN) may promote autophagy and alleviate carotid artery stenosis by reducing the expression of CDCP1. CDCP1 is upregulated in vascular smooth muscle cells within a carotid artery stenosis model, as demonstrated by studies conducted both in vivo and in vitro. Knocking down CDCP1 enhanced mitochondrial autophagy by upregulating ATG4A, leading to a reduction in reactive oxygen species (ROS) release and protection of cell viability. Moreover, both in vitro and in vivo experiments confirmed that 8-PN effectively decreases CDCP1 expression, activates cellular autophagy, and mitigates the progression of carotid artery stenosis. These findings highlight the importance ofCDCP1 in carotid artery stenosis and underscore the capability as a therapeutic option for this condition. Overall design: RNA-seq profiling of CDCP1 knockdown under Ang II treatment in vascular smooth muscle cells.