The OIP5 Antisense RNA 1/miR‐30b‐5p/RASA1 Axis Regulates Endothelial Senescence and Atherosclerosis Progression via Epigenetic Regulation

ABSTRACT Atherosclerosis is a major cause of cardiovascular diseases, and endothelial cells (ECs) senescence plays a key role in its initiation and progression. This study investigates the function and epigenetic regulatory mechanisms of long non‐coding RNA (lncRNA) OIP5 antisense RNA 1 (OIP5‐AS1) in oxidized low‐density lipoprotein (Ox‐LDL)‐induced senescence and atherosclerosis in human aortic endothelial cells (HAECs). The experiments show that Ox‐LDL stimulation upregulates the expression of OIP5‐AS1 and RASA1 while inhibiting miR‐30b‐5p. Silencing OIP5‐AS1 significantly suppresses the expression of senescence‐associated secretory phenotype (SASP) factors, alleviates HAECs senescence, and enhances proliferation, migration, and angiogenesis. Methylation‐specific primers (MSP) and bisulfite‐specific primers (BSP) analyses reveal that Ox‐LDL stimulation activates OIP5‐AS1 expression by reducing the DNA methylation level in its promoter region and altering histone modifications (increased H3K27ac and decreased H3K9me3). Luciferase assays show that OIP5‐AS1 acts as a competing endogenous RNA (ceRNA) by binding to miR‐30b‐5p and upregulating RASA1. Animal experiments further confirm that the knockdown of OIP5‐AS1 alleviates atherosclerosis in ApoE −/− mice. This study reveals the impact of the OIP5‐AS1/miR‐30b‐5p/RASA1 axis and its epigenetic regulation on atherosclerosis.