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

Balint, Brittany; Hergalant, Sébastien; Camadro, Jean‐Michel; Blaise, Sébastien; Vanalderwiert, Laetitia; Lignières, Laurent; Guéant-Rodríguez, Rosa-María; Guéant, Jean‐Louis

doi:10.1161/atvbaha.120.315587

Cited by 6 publications

(9 citation statements)

References 64 publications

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“…Elastin breaks were correlated to increased protease activities, including neutrophil elastase, cathepsin-K, cathepsin-S, MMP 9, and MMP2. 11 The long-term effects of fetal programming were related to increased expression of MARS (methionyl-tRNA synthetase) which is involved in irreversible protein homocysteinylation. 11 These data contribute to understanding why homocysteine-lowering B vitamin supplementation fails to relieve vascular complications in adulthood.…”

Section: Homocysteine Effects On the Medial Layer Of Large Arteriesmentioning

confidence: 99%

“…11 The long-term effects of fetal programming were related to increased expression of MARS (methionyl-tRNA synthetase) which is involved in irreversible protein homocysteinylation. 11 These data contribute to understanding why homocysteine-lowering B vitamin supplementation fails to relieve vascular complications in adulthood. The MDD-fetal programming also produces a cardiomyopathy linked to inflammation and fibrosis through angiotensin-AT2 and TGFB1 pathways, in addition to the alteration of energy metabolism.…”

Section: Homocysteine Effects On the Medial Layer Of Large Arteriesmentioning

confidence: 99%

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Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

et al. 2022

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Thromboembolic manifestations are relativement frequent in patients with intermediate/severe hyperhomocysteinemia (> 30 µmol/L) related to inherited disorders and deficiencies in vitamin B12 and folate. In contrast, moderate hyperhomocysteinemia (15- 30 µmol/L) is a modest predictor of cardiovascular risk. The recognition of homocysteine as a cardiovascular risk factor has been challenged by some but not all randomized clinical trials. We reviewed the main data of this controversy and formulated conclusions to be translated in clinical practice. Lowering homocysteine trials have been performed in cardiovascular subjects with moderate but not intermediate/severe hyperhomocysteinemia despite the dose-effect risk association. The first meta-analyses found no benefit and led cardiology societies not recommending homocysteine in the assessment of cardiovascular risk. This guideline challenged the need to diagnose and treat the nutritional and genetic causes of intermediate/major hyperhomocysteinemia and was not revised when larger meta-analyses concluded to a reduced risk of stroke. In a recent observational study, 84% of consecutive cardiovascular patients assessed for homocysteine had intermediate or major hyperhomocysteinemia, which was properly assessed in only half cases and related to B12 and/or folate deficiency and Addisson/Biermer disease in 55% of these cases. In conclusion, revisiting observational studies and clinical trials suggests that cardiovascular patients should be screened for hyperhomocysteinemia, when no other risk factor is found. Patients with intermediate/major hyperhomocysteinemia should be properly assessed and treated for vitamin B deficiencies and inherited disorders according to current guidelines. Further trials are needed to assess the lowering homocysteine effect according to hyperhomocysteinemia categories at baseline.

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Section: Homocysteine Effects On the Medial Layer Of Large Arteriesmentioning

confidence: 99%

Section: Homocysteine Effects On the Medial Layer Of Large Arteriesmentioning

confidence: 99%

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

et al. 2022

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“…We measured plasma EDP levels using a colorometric method and plasma desmosine levels by Elisa method (Fig. 3 G), as described previously in in the literature 28 . The results revealed increased plasma EDP and desmosine levels in the APL-KO mice as compared to those in the WT mice.…”

Section: Resultsmentioning

confidence: 99%

“…Evaluations of EDP concentrations were performed using a commercially available kit (Biocolor, Antrim, U.K.) according to Blaise et al 48 or a desmosine ELISA kit (Cusabio Technology LLC, Houston, TX, U.S.) according to Balin et al . 28 . A neutrophil elastase activity assay and cathepsin activity assay (Abcam, Cambridge, U.K.) were used to measure neutrophil elastase and cathepsin S activities, respectively, according to Romier et al 49 and Balint et al 28 .…”

Section: Methodsmentioning

confidence: 99%

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Apelin expression deficiency in mice contributes to vascular stiffening by extracellular matrix remodeling of the aortic wall

Romier

Dray

Vanalderwiert

et al. 2021

Sci Rep

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Numerous recent studies have shown that in the continuum of cardiovascular diseases, the measurement of arterial stiffness has powerful predictive value in cardiovascular risk and mortality and that this value is independent of other conventional risk factors, such as age, cholesterol levels, diabetes, smoking, or average blood pressure. Vascular stiffening is often the main cause of arterial hypertension (AHT), which is common in the presence of obesity. However, the mechanisms leading to vascular stiffening, as well as preventive factors, remain unclear. The aim of the present study was to investigate the consequences of apelin deficiency on the vascular stiffening and wall remodeling of aorta in mice. This factor freed by visceral adipose tissue, is known for its homeostasic role in lipid and vascular metabolisms, or again in inflammation. We compared the level of metabolic markers, inflammation of white adipose tissue (WAT), and aortic wall remodeling from functional and structural approaches in apelin-deficient and wild-type (WT) mice. Apelin-deficient mice were generated by knockout of the apelin gene (APL-KO). From 8 mice by groups, aortic stiffness was analyzed by pulse wave velocity measurements and by characterizations of collagen and elastic fibers. Mann–Whitney statistical test determined the significant data (p < 5%) between groups. The APL-KO mice developed inflammation, which was associated with significant remodeling of visceral WAT, such as neutrophil elastase and cathepsin S expressions. In vitro, cathepsin S activity was detected in conditioned medium prepared from adipose tissue of the APL-KO mice, and cathepsin S activity induced high fragmentations of elastic fiber of wild-type aorta, suggesting that the WAT secretome could play a major role in vascular stiffening. In vivo, remodeling of the extracellular matrix (ECM), such as collagen accumulation and elastolysis, was observed in the aortic walls of the APL-KO mice, with the latter associated with high cathepsin S activity. In addition, pulse wave velocity (PWV) and AHT were increased in the APL-KO mice. The latter could explain aortic wall remodeling in the APL-KO mice. The absence of apelin expression, particularly in WAT, modified the adipocyte secretome and facilitated remodeling of the ECM of the aortic wall. Thus, elastolysis of elastic fibers and collagen accumulation contributed to vascular stiffening and AHT. Therefore, apelin expression could be a major element to preserve vascular homeostasis.

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Consequences of the exposome to gestational diabetes mellitus

Rudge

Alves

Hallur

et al. 2023

Biochimica et Biophysica Acta (BBA) - General Subjects

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

Cited by 6 publications

References 64 publications

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

Hyperhomocysteinemia in Cardiovascular Diseases: Revisiting Observational Studies and Clinical Trials

Apelin expression deficiency in mice contributes to vascular stiffening by extracellular matrix remodeling of the aortic wall

Consequences of the exposome to gestational diabetes mellitus

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