CircDLGAP4 induces autophagy and improves endothelial cell dysfunction in atherosclerosis by targeting PTPN4 with...

Area of Science:

• Molecular Biology
• Cardiovascular Research
• RNA Biology

Background:

• Circular RNAs (circRNAs) are increasingly recognized for their roles in various diseases, including atherosclerosis (AS).
• circDLGAP4, a novel circRNA, has been identified and its expression is altered in AS pathogenesis.

Purpose of the Study:

• To investigate the role and mechanism of circDLGAP4 in atherosclerosis.
• To elucidate the regulatory axis circDLGAP4/miR-134-5p/PTPN4 in the context of AS.

Main Methods:

• Atherosclerosis models were established using oxidized low-density lipoprotein (ox-LDL) in human umbilical vein endothelial cells (HUVECs) and a high-fat diet in a mouse model.
• Functional assays were performed to assess the effects of circDLGAP4 on cell proliferation, autophagy, apoptosis, and inflammation in vitro and in vivo.
• Mechanism assays were conducted to explore the interaction between circDLGAP4, miR-134-5p, and PTPN4.

Main Results:

• CircDLGAP4 demonstrated protective effects by promoting proliferation and autophagy, while inhibiting apoptosis and inflammation in ox-LDL-treated HUVECs, thereby improving endothelial barrier function.
• CircDLGAP4 directly targets miR-134-5p, which in turn regulates PTPN4. Knockout of PTPN4 reversed the effects of circDLGAP4 or miR-134-5p manipulation.
• In vivo studies showed that reduced circDLGAP4 or increased miR-134-5p exacerbated AS phenotypes, including increased plaque area, reduced autophagy, and elevated inflammatory cytokines.

Conclusions:

• CircDLGAP4 plays a crucial protective role in AS by modulating autophagy and improving endothelial dysfunction.
• The circDLGAP4/miR-134-5p/PTPN4 axis represents a significant pathway involved in AS development and progression.
• This axis offers potential therapeutic targets for managing atherosclerosis.