Light deficiency in Apoe-/-mice increases atheroma plaque size and vulnerability by modulating local immunity
Por:
Hurtado-Genovés G, Herrero-Cervera A, Vinué A, Martín-Vañó S, Aguilar-Ballester M, Taberner-Cortés A, Jiménez-Martí E, Martínez-Hervás S, González-Navarro H
Publicada:
1 abr 2024
Ahead of Print:
1 feb 2024
Resumen:
Previous research suggests a potential involvement of the cytokine LIGHT (TNFSF14) in atherosclerosis. In this study, the genetic inactivation of Light in Apolipoprotein E deficient mice (male and female C57BL) augmented plaque size and vulnerability while decreasing Treg cells. Human and mouse transcriptomic results demonstrated deranged immune pathways in human atheromas with low LIGHT expression levels and in Light-deficient murine atheromas. In agreement with this, in vitro LIGHT-treatment of human lymphocytes, induced an elevation of Treg cell prevalence while proteomic analysis showed a downregulation of apoptotic and leukocyte cytotoxic pathways. Consistently, Light-deficient mouse lesions displayed increased plaque apoptosis and detrimental adventitial T-lymphocyte aggregates. Altogether suggested that LIGHT could promote a Treg prevalence in the local immunity to prevent the generation of vulnerable plaques via decreased cytotoxic microenvironment and apoptosis. Light gene delivery in Apoe-/-Light-/- mice, through bone marrow transplantation approaches, consistently diminished lesion size and restored local plaque immunity. Altogether demonstrate that Lightdeficiency promotes atheroma plaque progression, at least in part through local loss of immune homeostasis and increased apoptosis. This study suggest that therapies based on the local delivery of LIGHT within plaques might therefore prevent immune cell derangement and advanced atherosclerosis.
Filiaciones:
Hurtado-Genovés G:
INCL Biomed Res Inst, Valencia 46010, Spain
Herrero-Cervera A:
INCL Biomed Res Inst, Valencia 46010, Spain
Vinué A:
INCL Biomed Res Inst, Valencia 46010, Spain
Martín-Vañó S:
INCL Biomed Res Inst, Valencia 46010, Spain
Aguilar-Ballester M:
INCL Biomed Res Inst, Valencia 46010, Spain
Taberner-Cortés A:
INCL Biomed Res Inst, Valencia 46010, Spain
Jiménez-Martí E:
INCL Biomed Res Inst, Valencia 46010, Spain
Univ Valencia, Fac Med, Biochem & Mol Biol Dept, Valencia 46010, Spain
Martínez-Hervás S:
INCL Biomed Res Inst, Valencia 46010, Spain
Univ Valencia, Clin Hosp, Endocrinol & Nutr Dept, Valencia 46010, Spain
Univ Valencia, Dept Med, Valencia 46010, Spain
Inst Salud Carlos III, CIBER Diabet & Enfermedades Metab CIBERDEM, Madrid 28029, Spain
González-Navarro H:
INCL Biomed Res Inst, Valencia 46010, Spain
Univ Valencia, Fac Med, Biochem & Mol Biol Dept, Valencia 46010, Spain
Inst Salud Carlos III, CIBER Diabet & Enfermedades Metab CIBERDEM, Madrid 28029, Spain
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