| Arterial stiffening with ageing is associated with transforming growth factor-β1-related changes in adventitial collagen: reversal by aerobic exercise. | |
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MedLine Citation:
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PMID: 20807791 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We tested the hypothesis that carotid artery stiffening with ageing is associated with transforming growth factor-β1 (TGF-β1)-related increases in adventitial collagen and reductions in medial elastin, which would be reversed by voluntary aerobic exercise. Ex vivo carotid artery incremental stiffness was greater in old (29–32 months, n = 11) vs. young (4–7 months, n = 8) cage control B6D2F1 mice (8.84 ± 1.80 vs. 4.54 ± 1.18 AU, P < 0.05), and was associated with selective increases in collagen I and III and TGF-β1 protein expression in the adventitia (P < 0.05), related to an increase in smooth muscle α-actin (SMαA) (myofibroblast phenotype) (P < 0.05). In cultured adventitial fibroblasts, TGF-β1 induced increases in superoxide and collagen I protein (P < 0.05), which were inhibited by Tempol, a superoxide dismutase. Medial elastin was reduced with ageing, accompanied by decreases in the pro-synthetic elastin enzyme, lysyl oxidase, and increases in the elastin-degrading enzyme, matrix metalloproteinase 2. Fibronectin was unchanged with ageing, but there was a small increase in calcification (P < 0.05). Increased incremental stiffness in old mice was completely reversed (3.98 ± 0.34 AU, n = 5) by 10–14 weeks of modest voluntary wheel running (1.13 ± 0.29 km day−1), whereas greater voluntary wheel running (10.62 ± 0.49 km day−1) had no effect on young mice. The amelioration of carotid artery stiffness by wheel running in old mice was associated with reductions in collagen I and III and TGF-β1, partial reversal of the myofibroblast phenotype (reduced SMαA) and reduced calcification (all P < 0.05 vs. old controls), whereas elastin and its modulating enzymes were unaffected. Adventitial TGF-β1-related oxidative stress may play a key role in collagen deposition and large elastic artery stiffening with ageing and the efficacious effects of voluntary aerobic exercise. |
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Authors:
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Bradley S Fleenor; Kurt D Marshall; Jessica R Durrant; Lisa A Lesniewski; Douglas R Seals |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: The Journal of physiology Volume: 588 ISSN: 1469-7793 ISO Abbreviation: J. Physiol. (Lond.) Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-22 Completed Date: 2011-01-28 Revised Date: 2011-10-17 |
Medline Journal Info:
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Nlm Unique ID: 0266262 Medline TA: J Physiol Country: England |
Other Details:
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Languages: eng Pagination: 3971-82 Citation Subset: IM |
Affiliation:
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Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA. bradley.fleenor@colorado.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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metabolism*,
pathology Analysis of Variance Animals Carotid Artery Diseases / metabolism*, pathology Cells, Cultured Collagen / metabolism* Connective Tissue / metabolism, pathology Cyclic N-Oxides / pharmacology Elastin / metabolism Fibroblasts / cytology, drug effects, metabolism Fibronectins / metabolism Male Matrix Metalloproteinase 2 / metabolism Mice Myocytes, Smooth Muscle / cytology, drug effects, metabolism Physical Conditioning, Animal / physiology* Rats Rats, Sprague-Dawley Spin Labels Superoxides / metabolism Transforming Growth Factor beta1 / metabolism*, pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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AG000279/AG/NIA NIH HHS; AG013038/AG/NIA NIH HHS; AG033196/AG/NIA NIH HHS; HL007822/HL/NHLBI NIH HHS; K01 AG033196-03/AG/NIA NIH HHS; R21 AG033755-03/AG/NIA NIH HHS; R37 AG013038-16/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Cyclic N-Oxides; 0/Fibronectins; 0/Spin Labels; 0/Transforming Growth Factor beta1; 11062-77-4/Superoxides; 2226-96-2/tempol; 9007-34-5/Collagen; 9007-58-3/Elastin; EC 3.4.24.24/Matrix Metalloproteinase 2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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