Apolipoprotein A-1 Antisense RNA Exacerbates Atherosclerosis by Targeting MicroRNA-185

To investigate the expression of long non-coding RNA (lncRNA) apolipoprotein A-1 antisense RNA (APOA1-AS) in the serum of atherosclerosis (AS) patients and AS cell models, and its effects on cell proliferation, apoptosis, and underlying mechanisms. Twenty angiography-confirmed coronary atherosclerosis patients (≥ 50% stenosis, never treated) were enrolled, excluding comorbidities (hypertension, diabetes, organ dysfunction, or tumors). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect APOA1-AS and microRNA-185 (miR-185) in the serum of AS patients and healthy controls. AS cell models were created by treating human smooth muscle cells (HASMCs) with 100 mg/L oxidized low-density lipoprotein (ox-LDL) for 24 h. Cells were transfected with APOA1-AS small interfering RNA (si-APOA1-AS), miR-185 mimics, and si-APOA1-AS, followed by ox-LDL treatment. Cell proliferation was analyzed with Cell Counting Kit-8 (CCK8), and apoptosis with flow cytometry and Western blot. The interaction between APOA1-AS and miR-185 was confirmed by luciferase reporter assay. APOA1-AS and miR-185 levels were significantly higher in AS patients than in controls (P < 0.001). In ox-LDL-treated HASMCs, APOA1-AS and miR-185 expression increased (P < 0.001). APOA1-AS knockdown or miR-185 overexpression reduced proliferation and apoptosis, lowered Caspase3 and Bax, and elevated Bcl-2 (P < 0.001). APOA1-AS intervenes in the expression of miR-185 (P < 0.001) and directly binds miR-185 as a molecular sponge. This study identifies APOA1-AS as a novel AS biomarker and demonstrates its pathogenic role in vascular smooth muscle cells (VSMC) dysfunction via miR-185 sponging. The APOA1-AS/miR-185 axis links lipid metabolism to VSMC remodeling, offering a dual-target strategy for plaque stabilization.