LncRNA AC100865.1 regulates macrophage adhesion and ox-LDL intake through miR-7/GDF5 pathway.

Abstract

Objectives: Cardiovascular disease (CVD) accounts for over 40 % of deaths related to diseases among residents. Atherosclerosis (AS) and its associated thrombosis are the primary causes of CVD. LncRNA AC100865.1, a newly identified lncRNA, has shown potential as a diagnostic biomarker for AS. This study aims to evaluate the therapeutic value of lncRNA AC100865.1 in AS.

Methods: Real-time PCR was conducted to assess the relative expression of lncRNA AC100865.1 in Peripheral Blood Mononuclear Cell (PBMC) samples from 50 CVD patients and 50 healthy controls. lncRNA AC100865.1 was overexpressed in RAW264.7 cells to measure its effects on adhesion and oxidized low-density lipoprotein (ox-LDL) uptake. Flow cytometry was utilized to identify the pathway mediating these processes. The luciferase assay and knockout rescue experiments were performed to elucidate the downstream signaling pathways involved.

Results: lncRNA AC100865.1 expression was found to be downregulated in CVD patients. Overexpression of lncRNA AC100865.1 significantly enhanced the adhesion capacity of RAW264.7 cells. Luciferase reporter assays and flow cytometry indicated that this effect is mediated through the miR-7/GDF5/p38/LFA-1 pathway. Furthermore, lncRNA AC100865.1 notably increased ox-LDL uptake by macrophages via upregulation of CD36 expression.

Conclusion: Overexpression of lncRNA AC100865.1 enhances the adhesion of RAW264.7 cells through the miR-7/GDF5/p38/LFA-1 pathway and increases ox-LDL uptake by elevating CD36 levels. These findings suggest that circulating lncRNA AC100865.1 may serve not only as an early diagnostic marker for CVD but also as a potential therapeutic target, offering new prospects for CVD treatment.