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3 results on '"Martine Lelièvre-Pégorier"'

1. Long Lasting Microvascular Tone Alteration in Rat Offspring Exposed In Utero to Maternal Hyperglycaemia.

Author

Emilie Vessières, Abdallah Dib, Jennifer Bourreau, Eric Lelièvre, Marc-Antoine Custaud, Martine Lelièvre-Pégorier, Laurent Loufrani, Daniel Henrion, and Céline Fassot

Subjects
Medicine, Science
Abstract

Epidemiologic studies have demonstrated that cardiovascular risk is not only determined by conventional risk factors in adulthood, but also by early life events which may reprogram vascular function. To evaluate the effect of maternal diabetes on fetal programming of vascular tone in offspring and its evolution during adulthood, we investigated vascular reactivity of third order mesenteric arteries from diabetic mother offspring (DMO) and control mother offspring (CMO) aged 3 and 18 months. In arteries isolated from DMO the relaxation induced by prostacyclin analogues was reduced in both 3- and 18-month old animals although endothelium (acetylcholine)-mediated relaxation was reduced in 18-month old DMO only. Endothelium-independent (sodium nitroprusside) relaxation was not affected. Pressure-induced myogenic tone, which controls local blood flow, was reduced in 18-month old CMO compared to 3-month old CMO. Interestingly, myogenic tone was maintained at a high level in 18-month old DMO even though agonist-induced vasoconstriction was not altered. These perturbations, in 18-months old DMO rats, were associated with an increased pMLC/MLC, pPKA/PKA ratio and an activated RhoA protein. Thus, we highlighted perturbations in the reactivity of resistance mesenteric arteries in DMO, at as early as 3 months of age, followed by the maintenance of high myogenic tone in older rats. These modifications are in favour of excessive vasoconstrictor tone. These results evidenced a fetal programming of vascular functions of resistance arteries in adult rats exposed in utero to maternal diabetes, which could explain a re-setting of vascular functions and, at least in part, the occurrence of hypertension later in life.

Published
2016
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2. The magnitude of nephron number reduction mediates intrauterine growth-restriction-induced long term chronic renal disease in the rat. A comparative study in two experimental models

Author

Umberto Simeoni, Farid Boubred, Laurent Daniel, Christophe Buffat, Michel Tsimaratos, Martine Lelièvre-Pégorier, Charles Oliver, Nutrition, obésité et risque thrombotique (NORT), Institut National de la Recherche Agronomique (INRA)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Neonatology, University Hospital Marburg, Germany, Laboratoire de Biopathologie de l'Adhésion et de la Signalisation (EA3281), Université de la Méditerranée - Aix-Marseille 2, Laboratoire de Biologie médicale, AP-HM, Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Pediat Multidisciplinaire, Hôpital de la Timone [CHU - APHM] (TIMONE), Institut National de la Recherche Agronomique (INRA), Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche des Cordeliers (CRC), Université Pierre et Marie Curie - Paris 6 (UPMC)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), DOHaD Laboratory, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Université de Lausanne = University of Lausanne (UNIL), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Lausanne, Nutrition, obésité et risque thrombotique ( NORT ), Aix Marseille Université ( AMU ) -Institut National de la Recherche Agronomique ( INRA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Laboratoire de Biopathologie de l'Adhésion et de la Signalisation ( EA3281 ), Hôpital Sainte-Marguerite [CHU - APHM] ( Hôpitaux Sud ), Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut National de la Recherche Agronomique ( INRA ), Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre de Recherche des Cordeliers ( CRC ), Université Paris Diderot - Paris 7 ( UPD7 ) -École pratique des hautes études ( EPHE ) -Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Centre Hospitalier Universitaire Vaudois [Lausanne] ( CHUV ), Université Paris Diderot - Paris 7 (UPD7)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Aix Marseille Université (AMU)-Institut National de la Recherche Agronomique (INRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Boubred, Farid, Université Pierre et Marie Curie - Paris 6 (UPMC)-École pratique des hautes études (EPHE), and ProdInra, Archive Ouverte

Subjects
Male, insuffisance rénale, Prenatal glucocorticoids, poids faible de naissance, Intrauterine growth restriction, Blood Pressure, Nephron, 030204 cardiovascular system & hematology, Kidney, Kidney Function Tests, urologic and male genital diseases, Betamethasone, renal insufficiency, Rats, Sprague-Dawley, 0302 clinical medicine, IUGR, sclerosis, Chronic kidney disease, pulmonary hypertension, Medicine, Birth Weight, Low birth weight, Preterm infant, Nephron number, Hypertension, Glomerular sclerosis, Medicine(all), [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Fetal Growth Retardation, enfant prématuré, General Medicine, premature infant, female genital diseases and pregnancy complications, medicine.anatomical_structure, retard de croissance intrautérine, Female, maladie rénale, medicine.symptom, medicine.medical_specialty, hypertension, Offspring, Systole, Birth weight, Médecine humaine et pathologie, Renal function, 030209 endocrinology & metabolism, General Biochemistry, Genetics and Molecular Biology, sclérose, 03 medical and health sciences, Internal medicine, [ SDV.MHEP ] Life Sciences [q-bio]/Human health and pathology, glucocorticoïde, Animals, Renal Insufficiency, Chronic, Biochemistry, Genetics and Molecular Biology(all), business.industry, urogenital system, Research, Nephrons, medicine.disease, Endocrinology, Blood pressure, Animals, Newborn, Human health and pathology, glucocorticoid, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Background: Intrauterine growth restriction (IUGR) is a risk factor for hypertension (HT) and chronic renal disease (CRD). A reduction in the nephron number is proposed to be the underlying mechanism; however, the mechanism is debated. The aim of this study was to demonstrate that IUGR-induced HT and CRD are linked to the magnitude of nephron number reduction, independently on its cause. Methods: Systolic blood pressure (SBP), glomerular filtration rate (GFR), proteinuria, nephron number, and glomerular sclerosis were compared between IUGR offspring prenatally exposed to a maternal low-protein diet (9% casein; LPD offspring) or maternal administration of betamethasone (from E17 to E19; BET offspring) and offspring with a normal birth weight (NBW offspring). Results: Both prenatal interventions led to IUGR and a similar reduction in birth weight. In comparison to NBW offspring, BET offspring had a severe nephron deficit (-50% in males and -40% in females, p < 0.01), an impaired GFR (-33%, p < 0.05), and HT (SBP+ 17 mmHg, p < 0.05). Glomerular sclerosis was more than twofold higher in BET offspring than in NBW offspring (p < 0.05). Long-term SBP, GFR, and glomerular sclerosis were unchanged in LPD offspring while the nephron number was moderately reduced only in males (-28% vs. NBW offspring, p < 0.05). Conclusion: In this study, the magnitude of nephron number reduction influences long term renal disease in IUGR offspring: a moderate nephron number is an insufficient factor. Extremely long-term follow-up of adults prenatally exposed to glucocorticoids are required.

Published
2016

3. Long Lasting Microvascular Tone Alteration in Rat Offspring Exposed In Utero to Maternal Hyperglycaemia

Author

Laurent Loufrani, Marc-Antoine Custaud, Abdallah Dib, Daniel Henrion, Jennifer Bourreau, Emilie Vessieres, Eric Lelièvre, Céline Fassot, Martine Lelièvre-Pégorier, Biologie Neurovasculaire et Mitochondriale Intégrée, Université d'Angers ( UA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Cardiovascular Functions In Vitro ( CARFI ), Centre de Recherche des Cordeliers ( CRC (UMR_S 872) ), Université Pierre et Marie Curie - Paris 6 ( UPMC ) -Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Cardiovascular Functions In Vitro (CARFI), Centre de Recherche des Cordeliers (CRC (UMR_S 872)), Université Paris Descartes - Paris 5 (UPD5)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Autonomous intelligent machine (MAIA), Inria Nancy - Grand Est, Institut National de Recherche en Informatique et en Automatique (Inria)-Institut National de Recherche en Informatique et en Automatique (Inria)-Department of Complex Systems, Artificial Intelligence & Robotics (LORIA - AIS), Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Laboratoire Lorrain de Recherche en Informatique et ses Applications (LORIA), Institut National de Recherche en Informatique et en Automatique (Inria)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Senescence escape and soluble markers of cancer progression (CRCINA - Département ONCO - Equipe 12), Centre de recherche de Cancérologie et d'Immunologie / Nantes - Angers (CRCINA), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biologie Neurovasculaire Intégrée (BNVI), Hémodynamique, Interaction Fibrose et Invasivité tumorales Hépatiques (HIFIH), Université d'Angers (UA), Physiologie et pharmacologie vasculaire et rénale, IFR58-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), and HAL-UPMC, Gestionnaire

Subjects
0301 basic medicine, genetic structures, lcsh:Medicine, Blood Pressure, Vasodilation, Prostacyclin, 030204 cardiovascular system & hematology, Rats, Sprague-Dawley, 0302 clinical medicine, Pregnancy, lcsh:Science, Mesenteric arteries, ComputingMilieux_MISCELLANEOUS, Multidisciplinary, [ SDV.MHEP.CSC ] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Mesenteric Arteries, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, medicine.anatomical_structure, In utero, Prenatal Exposure Delayed Effects, Female, Sodium nitroprusside, medicine.symptom, Research Article, medicine.drug, medicine.medical_specialty, Endothelium, Offspring, In Vitro Techniques, Diabetes Mellitus, Experimental, 03 medical and health sciences, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Internal medicine, medicine, [SDV.MHEP.PHY]Life Sciences [q-bio]/Human health and pathology/Tissues and Organs [q-bio.TO], Animals, business.industry, Body Weight, lcsh:R, Epoprostenol, 030104 developmental biology, Endocrinology, Animals, Newborn, Vasoconstriction, Hyperglycemia, Microvessels, lcsh:Q, business
Abstract

International audience; Epidemiologic studies have demonstrated that cardiovascular risk is not only determined by conventional risk factors in adulthood, but also by early life events which may reprogram vascular function. To evaluate the effect of maternal diabetes on fetal programming of vas-cular tone in offspring and its evolution during adulthood, we investigated vascular reactivity of third order mesenteric arteries from diabetic mother offspring (DMO) and control mother offspring (CMO) aged 3 and 18 months. In arteries isolated from DMO the relaxation induced by prostacyclin analogues was reduced in both 3-and 18-month old animals although endothelium (acetylcholine)-mediated relaxation was reduced in 18-month old DMO only. Endothelium-independent (sodium nitroprusside) relaxation was not affected. Pressure-induced myogenic tone, which controls local blood flow, was reduced in 18-month old CMO compared to 3-month old CMO. Interestingly, myogenic tone was maintained at a high level in 18-month old DMO even though agonist-induced vasoconstriction was not altered. These perturbations, in 18-months old DMO rats, were associated with an increased pMLC/MLC, pPKA/PKA ratio and an activated RhoA protein. Thus, we highlighted perturbations in the reactivity of resistance mesenteric arteries in DMO, at as early as 3 months of age, followed by the maintenance of high myogenic tone in older rats. These modifications are in favour of excessive vasoconstrictor tone. These results evi-denced a fetal programming of vascular functions of resistance arteries in adult rats exposed in utero to maternal diabetes, which could explain a re-setting of vascular functions and, at least in part, the occurrence of hypertension later in life.

Published
2016

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