Fetal Programming by Methyl Donor Deficiency Produces Pathological Remodeling of the Ascending Aorta.
Fiche publication
Date publication
avril 2021
Journal
Arteriosclerosis, thrombosis, and vascular biology
Auteurs
Membres identifiés du Cancéropôle Est :
Dr BLAISE Sébastien, Pr GUEANT Jean-Louis
Tous les auteurs :
Balint B, Hergalan S, Camadro JM, Blaise S, Vanalderwiert L, Lignières L, Guéant-Rodriguez RM, Guéant JL
Lien Pubmed
Résumé
Deficiency in vitamin B12/folate (methyl donor deficiency [MDD]) produces cardiovascular outcomes during aging and fetal programming effects in newborns of MDD mothers. Whether fetal programming provokes long-term effects on aorta remains largely unknown. Approach and Results: We investigated the impact of fetal programming on ascending aorta of aged rats born from mothers subjected to MDD during gestation/lactation. We performed morphological and molecular examinations of ascending aorta in 21 days- and 400 days-aged rats with initial MDD fetal programming (initial MDD) compared with control matched rats. Initial MDD induces remodeling of ascending aorta in aged rats, with collagen deposition (=0.0008), decreased thickness of elastin (<0.0001), and 8.7-fold increase of elastin breaks (=0.0002). Proteomic analyses, Western blotting, and immunohistochemical examination revealed decreased expression of α-smooth muscle actin, vinculin, SM22α (smooth muscle 22α), and N-cadherin and increased expression of TGF (transforming growth factor) β1. Elastin breaks were correlated to increased neutrophil elastase (=0.0002), cathepsin-K (=0.0002), cathepsin-S (<0.0001), and MMP (matrix metalloproteinase) 9, and MMP2 (<0.0001 and =0.02). Proximity Duolink ligation assay showed homocysteinylation of actin-associated and extracellular matrix proteins, including SM22α (=0.01), N-cadherin (=0.0008), and vinculin (=0.001), which was associated with elastin breaks (=0.002) and increased expression of MARS (methionyl-tRNA synthetase; involved in irreversible protein homocysteinylation). Furthermore, we observed an inverse relationship between elastin breaks and blood pressure (systolic, =0.004 and diastolic, =0.0007).
Mots clés
aorta, blood pressure, extracellular matrix, homocysteine, vinculin
Référence
Arterioscler Thromb Vasc Biol. 2021 Apr 8;:ATVBAHA120315587