One carbon metabolism, a complex metabolic network involved in pathomechanisms of inherited disorders, birth defects and age-related pathologies

Guéant, Jean‐Louis

doi:10.1016/j.biochi.2016.05.008

Biochimie

2016

DOI: 10.1016/j.biochi.2016.05.008

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One carbon metabolism, a complex metabolic network involved in pathomechanisms of inherited disorders, birth defects and age-related pathologies

Jean‐Louis Guéant

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2021

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Cited by 1 publication

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“…12 The one-carbon metabolism is a complex network of interconnected pathways that is regulated by a number of genes and depends on coenzymes issued from methyl donors, including folate and vitamin B12. 13,14 Interestingly, conditions leading to deficits in methyl donors during pregnancy have been implicated in the predisposition of metabolic conditions in offspring, including cardiovascular disease. 12 Whether fetal programming by methyl donor deficiency (MDD) leads to remodeling of large arteries, and in particular of the aorta, has yet to be determined.…”

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Fetal Programming by Methyl Donor Deficiency Produces Pathological Remodeling of the Ascending Aorta

Balint

Hergalant

Camadro

et al. 2021

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Objective: 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 ( P =0.0008), decreased thickness of elastin ( P <0.0001), and 8.7-fold increase of elastin breaks ( P =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 ( P =0.0002), cathepsin-K ( P =0.0002), cathepsin-S ( P <0.0001), and MMP (matrix metalloproteinase) 9, and MMP2 ( P <0.0001 and P =0.02). Proximity Duolink ligation assay showed homocysteinylation of actin-associated and extracellular matrix proteins, including SM22α ( P =0.01), N-cadherin ( P =0.0008), and vinculin ( P =0.001), which was associated with elastin breaks ( P =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, P =0.004 and diastolic, P =0.0007). Conclusions: MDD fetal programming produced altered integrity and remodeling of ascending aorta during aging and irreversible MARS-associated homocysteinylation of key proteins of extracellular matrix and elastin homeostasis. This contributes to understanding why homocysteine-lowering vitamin B supplementation fails to relieve vascular complications in adulthood.

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mentioning

confidence: 99%

Fetal Programming by Methyl Donor Deficiency Produces Pathological Remodeling of the Ascending Aorta

Balint

Hergalant

Camadro

et al. 2021

ATVB

Self Cite

View full text Add to dashboard Cite

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One carbon metabolism, a complex metabolic network involved in pathomechanisms of inherited disorders, birth defects and age-related pathologies

Cited by 1 publication

References 17 publications

Fetal Programming by Methyl Donor Deficiency Produces Pathological Remodeling of the Ascending Aorta

Fetal Programming by Methyl Donor Deficiency Produces Pathological Remodeling of the Ascending Aorta

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