Work

Loss of DNA Polymerase β Delays Atherosclerosis in ApoE−/− Mice Due to Inhibition of Vascular Smooth Muscle Cell Migration

Year: 2024

Type: article

Abstract: Atherosclerosis (AS) is an inflammatory disease characterized by arterial inflammation. One important trigger for AS development is the excessive migration of vascular smooth muscle cells (VSMCs); however, the mechanism underlying this phenomenon remains unclear. Therefore, we investigated the role of DNA polymerase β (Pol β), a crucial enzyme involved in base excision repair, VSMC migration, and subsequent AS development. In this study, we revealed a significant increase in Pol β content within AS plaques in ApoE−/−Pol β+/+ mice. In vitro experiments demonstrated a significant decrease in hCASMC viability and migration ability upon Pol β knockdown, whereas the subsequent recovery of Pol β expression reversed this effect. Moreover, our investigations revealed that Pol β knockdown leads to the inhibition of the POSTN gene transcription by suppressing the YY1/TGF-β1 pathway, resulting in the decreased expression of the protein periostin during VSMC migration. Collectively, our findings provide insights into the role of Pol β in AS development, offering a novel approach for the clinical treatment of cardiovascular diseases.

Source: International Journal of Molecular Sciences

DOI: 10.3390/ijms252111778