Abstract

Atherosclerotic cardiovascular disease, a leading cause of global mortality and morbidity, is driven by chronic inflammation and metabolic dysregulation. The inhibition of monocyte-macrophage inflammatory responses is a critical therapeutic strategy, as these cells play a central role in atherosclerosis progression. Glycolysis, a universal metabolic pathway, is regulated by the bifunctional enzyme PFKFB3, which modulates intracellular levels of fructose‑ 2,6‑bisphosphate (Fru‑2,6‑BP). Despite the potential of PFKFB3 inhibitors like 3PO in atherosclerosis treatment, their mechanisms and therapeutic efficacy remain incompletely understood. This study investigates the role of PFKFB3 inhibition in atherosclerosis using ApoE^‑/‑^ mice, highlighting its impact on monocyte‑macrophage responses and plaque formation. Our findings suggest that 3PO-mediated PFKFB3 inhibition attenuates atherosclerosis by reducing inflammatory markers and vascular remodeling, offering a promising therapeutic avenue.

Keywords: PFKFB3; 3PO; Coronary atherosclerosis; Glycolysis; Monocyte-macrophage; Inflammatory response