Phosphoglycerate Mutase 5 Is Important Mediator for Instigating Arterial Lipid Accumulation and Aggravating Atherosclerosis

Although the receptor-interacting protein kinase-3 (RIPK3)-phosphoglycerate mutase 5 (PGAM5) signaling pathway is activated in other disease models, its role in atherosclerotic lesions remains unclear. This study reveals that phosphorylated RIPK3 and PGAM5 expressions are significantly elevated within macrophages in atherosclerosis lesions of humans and mice. Overexpression of PGAM5 aggravates the atherosclerotic lesion in in vivo and in vitro models. PGAM5 knockdown in macrophages promotes angiopoietin-like 3 (ANGPTL3) gene and protein expression, reduces inflammatory factor release, and inhibits inflammation and migration in endothelial and smooth muscle cells by cellular communication. This study suggests PGAM5 as a crucial mediator in atherosclerosis and a potential therapeutic target for future treatments.