Phosphoglycerate Mutase 5 Is Important Mediator for Instigating Arterial Lipid Accumulation and Aggravating Atherosclerosis
Year: 2025
Type: article
Abstract: • PGAM5 is highly expressed in the atherosclerotic lesions of humans and ApoE −/− mice, as well as ox-LDL-exposed macrophages. • PGAM5 overexpression impedes the beneficial effects of RIPK3 inhibitor and aggravates the progression of atherosclerosis. • PGAM5 deficiency in macrophages leads to an increase in transcription and translation of the ANGPTL3 gene and reduces the release of inflammatory factors from macrophages, thereby preventing cross-talk between macrophages and ECs or SMCs. • PGAM5 is considered as a crucial mediator for affecting atherosclerotic lesions and a potentially important future therapeutic target for preventing cross-talk of vascular cells and ameliorating lesions. 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.
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,750
OpenAlex ID: W4408357252