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

Autor: Sébastien Blaise, Jean-Louis Guéant, Jean-Michel Camadro, Sébastien Hergalant, Laetitia Vanalderwiert, Rosa-Maria Guéant-Rodriguez, Brittany Balint, Laurent Lignières
Přispěvatelé: Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Institut Jacques Monod (IJM (UMR_7592)), Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), The study is part of the project entitled GEENAGE (Functional Genomic, Epigenomic and Environment Interplay to Impact the Understanding, Diagnosis and Management of Healthy and Pathological Ageing) of the University of Excellence I-Site LUE (Lorraine University of Excellence) referenced ANR-15-IDEX04-LUE funded by the French Ministry for research and higher education. The work was also supported by funding from the FHU ARRIMAGEF (Fédération Hospitalo-Universitaire Assessment and Integrative Research on RemodelingInflammation-Metabolic Stress in Systemic and Hepatogastrointestinal Metabolic Diseases), Inserm, European funds FEDER (Fond Européen de Développement Régional), and the Région Grand Est (project OMAGE), France., IMPACT GEENAGE, ANR-15-IDEX-0004,LUE,Isite LUE(2015)
Jazyk: angličtina
Rok vydání: 2021
Předmět:
0301 basic medicine
MESH: Extracellular Matrix Proteins
Pathology
Homocysteine
MESH: Vitamin B 12 Deficiency
MESH: Folic Acid Deficiency
[SDV]Life Sciences [q-bio]
MESH: Aortic Diseases
030204 cardiovascular system & hematology
Extracellular matrix
Fetal Development
chemistry.chemical_compound
0302 clinical medicine
MESH: Pregnancy
Pregnancy
MESH: Gestational Age
MESH: Gene Expression Regulation
Developmental
MESH: Animals
2. Zero hunger
Extracellular Matrix Proteins
biology
Gene Expression Regulation
Developmental
blood pressure
MESH: Aorta
Vinculin
MESH: Maternal Nutritional Physiological Phenomena
Prenatal Exposure Delayed Effects
Animal Nutritional Physiological Phenomena
Female
Cardiology and Cardiovascular Medicine
MESH: Vascular Remodeling
MESH: Fetal Development
medicine.medical_specialty
MESH: Peptide Hydrolases
extracellular matrix
Aortic Diseases
Gestational Age
Folic Acid Deficiency
Vascular Remodeling
MESH: Prenatal Exposure Delayed Effects
03 medical and health sciences
[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
medicine.artery
[SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Genomics [q-bio.GN]
Ascending aorta
medicine
[SDV.MHEP.AHA]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
[SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO]
Animals
MESH: Homocysteine
Fetal programming
Rats
Wistar
[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Biochemistry [q-bio.BM]
Pathological
Aorta
business.industry
vinculin
Vitamin B 12 Deficiency
[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry
Molecular Biology/Molecular biology
MESH: Rats
Wistar
Maternal Nutritional Physiological Phenomena
homocysteine
Disease Models
Animal
aorta
030104 developmental biology
Blood pressure
MESH: Animal Nutritional Physiological Phenomena
chemistry
biology.protein
MESH: Disease Models
Animal
[INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM]
business
MESH: Female
[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Peptide Hydrolases
Zdroj: Arteriosclerosis, Thrombosis, and Vascular Biology
Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2021, 41 (6), pp.1928-1941. ⟨10.1161/atvbaha.120.315587⟩
Arteriosclerosis, Thrombosis, and Vascular Biology, American Heart Association, 2021, 41 (6), pp.1928-1941. ⟨10.1161/ATVBAHA.120.315587⟩
ISSN: 1079-5642
1524-4636
Popis: 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 aortas in 21 days- and 400 days-aged rats with initial MDD fetal programming (iMDD) compared with control matched rats. iMDD induces remodeling of the ascending aorta in aged rats, with collagen deposition ( P =0.0008), decreased thickness of elastin ( P 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 P 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.
Databáze: OpenAIRE
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