{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:36:36Z","timestamp":1790742996431,"version":"4.1.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>\n              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 (\n              <jats:italic>P<\/jats:italic>\n              =0.0008), decreased thickness of elastin (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001), and 8.7-fold increase of elastin breaks (\n              <jats:italic>P<\/jats:italic>\n              =0.0002). Proteomic analyses, Western blotting, and immunohistochemical examination revealed decreased expression of \u03b1-smooth muscle actin, vinculin, SM22\u03b1 (smooth muscle 22\u03b1), and N-cadherin and increased expression of TGF (transforming growth factor) \u03b21. Elastin breaks were correlated to increased neutrophil elastase (\n              <jats:italic>P<\/jats:italic>\n              =0.0002), cathepsin-K (\n              <jats:italic>P<\/jats:italic>\n              =0.0002), cathepsin-S (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001), MMP (matrix metalloproteinase) 9, and MMP2 (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.0001 and\n              <jats:italic>P<\/jats:italic>\n              =0.02). Proximity Duolink ligation assay showed homocysteinylation of actin-associated and extracellular matrix proteins, including SM22\u03b1 (\n              <jats:italic>P<\/jats:italic>\n              =0.01), N-cadherin (\n              <jats:italic>P<\/jats:italic>\n              =0.0008), and vinculin (\n              <jats:italic>P<\/jats:italic>\n              =0.001), which was associated with elastin breaks (\n              <jats:italic>P<\/jats:italic>\n              =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,\n              <jats:italic>P<\/jats:italic>\n              =0.004 and diastolic,\n              <jats:italic>P<\/jats:italic>\n              =0.0007).\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>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.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.120.315587","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T09:05:34Z","timestamp":1617872734000},"page":"1928-1941","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":12,"title":["Fetal Programming by Methyl Donor Deficiency Produces Pathological Remodeling of the Ascending Aorta"],"prefix":"10.1161","volume":"41","author":[{"given":"Brittany","family":"Balint","sequence":"first","affiliation":[{"name":"UMR Inserm 1256 N-GERE (Nutrition, G\u00e9netique et Exposition aux Risques Environmentaux) (B.B., S.H., R.-M.G.-R., J.-L.G.), Universit\u00e9 de Lorraine, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8456-7992","authenticated-orcid":true,"given":"S\u00e9bastien","family":"Hergalant","sequence":"additional","affiliation":[{"name":"UMR Inserm 1256 N-GERE (Nutrition, G\u00e9netique et Exposition aux Risques Environmentaux) (B.B., S.H., R.-M.G.-R., J.-L.G.), Universit\u00e9 de Lorraine, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8549-2707","authenticated-orcid":true,"given":"Jean-Michel","family":"Camadro","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Institut Jacques Monod, UMR 7592, Universit\u00e9 Paris Diderot, CNRS, Sorbonne Paris Cit\u00e9, France (J.-M.C., L.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00e9bastien","family":"Blaise","sequence":"additional","affiliation":[{"name":"UMR CNRS (S.B., L.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Vanalderwiert","sequence":"additional","affiliation":[{"name":"UMR CNRS (S.B., L.V.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9893-501X","authenticated-orcid":true,"given":"Laurent","family":"Ligni\u00e8res","sequence":"additional","affiliation":[{"name":"Mass Spectrometry Laboratory, Institut Jacques Monod, UMR 7592, Universit\u00e9 Paris Diderot, CNRS, Sorbonne Paris Cit\u00e9, France (J.-M.C., L.L.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1402-3716","authenticated-orcid":true,"given":"Rosa-Maria","family":"Gu\u00e9ant-Rodriguez","sequence":"additional","affiliation":[{"name":"UMR Inserm 1256 N-GERE (Nutrition, G\u00e9netique et Exposition aux Risques Environmentaux) (B.B., S.H., R.-M.G.-R., J.-L.G.), Universit\u00e9 de Lorraine, France."},{"name":"Department of Molecular Medicine 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