circ_0006476 Modulates Atherosclerotic Macrophage Apoptosis Through the miR-3074-5p/DLL4 Axis: Implications for Notch Signaling Pathway Regulation in Cardiovascular Disease

As the population ages, atherosclerosis (AS), a major cause of cardiovascular disease (CVD), continues to rise. There is a common mechanism of action for circular RNAs (circRNAs) that involves the sponging of microRNAs (miRNAs) by binding to the miRNA response element (MRE), thereby increasing the transcription of their target messenger RNAs (mRNAs). Most diseases have been demonstrated to be profoundly reliant on circRNA. However, the underlying mechanism of circRNA in AS has yet to be understood clearly. Analyzing all differentially expressed circRNAs (DEcircRNAs), miRNAs (DEmiRNAs), and mRNAs (DEmRNAs) and their expression levels was conducted by full transcriptome sequencing on samples from both the Control and Nicotine groups. GO and KEGG analysis determined that nicotine affects the physiological processes and related pathways of macrophages. Molecular biology experiments were employed to validate a ceRNA regulatory network. The Notch signaling pathway is activated in nicotine-treated macrophages, and DLL4 on the pathway is upgraded. circ_0006476 is involved in apoptosis via miR-3074-5p/DLL4, regulating pathogenic processes related to the Notch signaling pathway. The better we understand the pathways for macrophage apoptosis, the more likely we will be to find other novel therapeutic targets that can help treat, prevent, and reduce the mortality associated with AS.