title: Remodeling of aorta extracellular matrix as a result of transient high oxygen exposure in newborn rats: implication for arterial rigidity and hypertension risk.
abstract: Neonatal high-oxygen exposure leads to elevated blood pressure, microvascular rarefaction, vascular dysfunction and arterial (aorta) rigidity in adult rats. Whether structural changes are present in the matrix of aorta wall is unknown. Considering that elastin synthesis peaks in late fetal life in humans, and early postnatal life in rodents, we postulated that transient neonatal high-oxygen exposure can trigger premature vascular remodelling. Sprague Dawley rat pups were exposed from days 3 to 10 after birth to 80% oxygen (vs. room air control) and were studied at 4 weeks. Blood pressure and vasomotor response of the aorta to angiotensin II and to the acetylcholine analogue carbachol were not different between groups. Vascular superoxide anion production was similar between groups. There was no difference between groups in aortic cross sectional area, smooth muscle cell number or media/lumen ratio. In oxygen-exposed rats, aorta elastin/collagen content ratio was significantly decreased, the expression of elastinolytic cathepsin S was increased whereas collagenolytic cathepsin K was decreased. By immunofluorescence we observed an increase in MMP-2 and TIMP-1 staining in aortas of oxygen-exposed rats whereas TIMP-2 staining was reduced, indicating a shift in the balance towards degradation of the extra-cellular matrix and increased deposition of collagen. There was no significant difference in MMP-2 activity between groups as determined by gelatin zymography. Overall, these findings indicate that transient neonatal high oxygen exposure leads to vascular wall alterations (decreased elastin/collagen ratio and a shift in the balance towards increased deposition of collagen) which are associated with increased rigidity. Importantly, these changes are present prior to the elevation of blood pressure and vascular dysfunction in this model, and may therefore be contributory.
authors.affiliation: Sainte-Justine University Hospital Research Center, Department of Paediatrics, Université de Montréal, Montreal, Québec, Canada.
authors.forename: Fanny
authors.initials: F
authors.lastname: Huyard
authors.affiliation: Sainte-Justine University Hospital Research Center, Department of Paediatrics, Université de Montréal, Montreal, Québec, Canada.
authors.forename: Catherine
authors.initials: C
authors.lastname: Yzydorczyk
authors.affiliation: Departments of Pediatrics & Pharmacology, Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Michele M
authors.initials: MM
authors.lastname: Castro
authors.affiliation: Sainte-Justine University Hospital Research Center, Department of Paediatrics, Université de Montréal, Montreal, Québec, Canada.
authors.forename: Anik
authors.initials: A
authors.lastname: Cloutier
authors.affiliation: Sainte-Justine University Hospital Research Center, Department of Paediatrics, Université de Montréal, Montreal, Québec, Canada.
authors.forename: Mariane
authors.initials: M
authors.lastname: Bertagnolli
authors.affiliation: Sainte-Justine University Hospital Research Center, Department of Pathology, Université de Montréal, Montreal, Québec, Canada.
authors.forename: Hervé
authors.initials: H
authors.lastname: Sartelet
authors.affiliation: Sainte-Justine University Hospital Research Center, Department of Paediatrics, Université de Montréal, Montreal, Québec, Canada.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Germain
authors.affiliation: Unit of Human Nutrition UMR 1019, INRA, Research Centre of Clermont-Ferrand/Theix, Saint-Genès-Champanelle, France.
authors.forename: Blandine
authors.initials: B
authors.lastname: Comte
authors.affiliation: Departments of Pediatrics & Pharmacology, Cardiovascular Research Centre, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Richard
authors.initials: R
authors.lastname: Schulz
authors.affiliation: Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.
authors.forename: Denis
authors.initials: D
authors.lastname: DeBlois
authors.affiliation: Sainte-Justine University Hospital Research Center, Department of Paediatrics, Université de Montréal, Montreal, Québec, Canada.
authors.forename: Anne Monique
authors.initials: AM
authors.lastname: Nuyt
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001011:Aorta / Q000187:drug effects* / Q000294:innervation / Q000473:pathology*; D001794:Blood Pressure / Q000187:drug effects; D003094:Collagen / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004549:Elastin / Q000378:metabolism; D005109:Extracellular Matrix / Q000187:drug effects* / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D020782:Matrix Metalloproteinases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010100:Oxygen / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012306:Risk; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors; D066253:Vascular Remodeling / Q000187:drug effects*; D059289:Vascular Stiffness / Q000187:drug effects*; D014666:Vasomotor System / Q000187:drug effects / Q000503:physiopathology
chemical_list: D013481:Superoxides; D003094:Collagen; D004549:Elastin; D020782:Matrix Metalloproteinases; D010100:Oxygen
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