Pyruvate Carboxylase in Macrophages Aggravates Atherosclerosis by Regulating Metabolism Reprogramming to Promote Inflammatory Responses Through the Hypoxia‐Inducible Factor‐1 Signaling Pathway DOI Creative Commons

Lingna Zhao,

Rongchang Wang,

Ran‐Xin Liu

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: May 20, 2025

Abstract Atherosclerosis (AS) is a major cause of cardiovascular diseases, driven by chronic inflammation and macrophage polarization toward proinflammatory phenotype. Pyruvate carboxylase (PC), mitochondrial enzyme involved in glucose metabolism, implicated various metabolic disorders; however, its role AS remains unclear. This study aims to investigate the mechanism PC on macrophages AS. upregulated humans mice with Myeloid cell‐specific knockout are generated effects deletion atherosclerotic plaque formation. deficiency mitigates high‐fat diet‐induced lesions apolipoprotein E injected adeno‐associated virus‐ PCSK9 DY . enhances respiration reduces glycolytic activity, thereby reducing reactive oxygen species overproduction damage macrophages. activates hypoxia‐inducible factor‐1 (HIF‐1) signaling pathway through reprogramming. induces nuclear translocation HIF‐1α aortic roots preventing from proteasome degradation. stabilizer reverses anti‐inflammatory effect macrophage‐PC ablation atherogenesis; inhibiting suppresses phenotype induced overexpression. indicates that aggravates reprogramming, promoting inflammatory responses HIF‐1 pathway.

Language: Английский

Multimodal Metabolomic Analysis Reveals Novel Metabolic Disturbances in Adults With Early Treated Phenylketonuria DOI Creative Commons
Yann Dos Santos, Patrick Emond, Ida Vanessa Döederlein Schwartz

et al.

JIMD Reports, Journal Year: 2025, Volume and Issue: 66(2)

Published: March 1, 2025

ABSTRACT Phenylketonuria (PKU) is an inborn error of metabolism responsible for accumulation phenylalanine, which leads to cognitive and developmental disorders if left untreated. Most studies adult PKU focus on neuropsychiatric complications, but new questions have been raised about systemic manifestations in adulthood. Fifteen adults with classic poor metabolic control 15 matched healthy controls were recruited compare their blood metabolomes by untargeted multimodal approach (polar, apolar, lipids) LC/MS a targeted the tryptophan pathway. Targeted analysis revealed serotonin hypometabolism aberrant kynurenine metabolism, as well potential implication microbiota differences some indole compounds compared controls. Untargeted confirms previous findings regarding TCA cycle, alanine aspartate glutamate arginine proline perturbations such biosynthesis or glyoxylate dicarboxylate metabolism. Future involving larger numbers patients varying degrees are needed confirm these findings.

Language: Английский

Citations

0
Pyruvate Carboxylase in Macrophages Aggravates Atherosclerosis by Regulating Metabolism Reprogramming to Promote Inflammatory Responses Through the Hypoxia‐Inducible Factor‐1 Signaling Pathway DOI Creative Commons

Lingna Zhao,

Rongchang Wang,

Ran‐Xin Liu

et al.

Advanced Science, Journal Year: 2025, Volume and Issue: unknown

Published: May 20, 2025

Abstract Atherosclerosis (AS) is a major cause of cardiovascular diseases, driven by chronic inflammation and macrophage polarization toward proinflammatory phenotype. Pyruvate carboxylase (PC), mitochondrial enzyme involved in glucose metabolism, implicated various metabolic disorders; however, its role AS remains unclear. This study aims to investigate the mechanism PC on macrophages AS. upregulated humans mice with Myeloid cell‐specific knockout are generated effects deletion atherosclerotic plaque formation. deficiency mitigates high‐fat diet‐induced lesions apolipoprotein E injected adeno‐associated virus‐ PCSK9 DY . enhances respiration reduces glycolytic activity, thereby reducing reactive oxygen species overproduction damage macrophages. activates hypoxia‐inducible factor‐1 (HIF‐1) signaling pathway through reprogramming. induces nuclear translocation HIF‐1α aortic roots preventing from proteasome degradation. stabilizer reverses anti‐inflammatory effect macrophage‐PC ablation atherogenesis; inhibiting suppresses phenotype induced overexpression. indicates that aggravates reprogramming, promoting inflammatory responses HIF‐1 pathway.

Language: Английский

Citations

0