We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Arterial stiffening with ageing is associated with transforming growth factor-β1-related changes in adventitial collagen: reversal by aerobic exercise.
- Authors
Fleenor, Bradley S.; Marshall, Kurt D.; Durrant, Jessica R.; Lesniewski, Lisa A.; Seals, Douglas R.
- Abstract
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.
- Publication
Journal of Physiology, 2010, Vol 588, Issue 20, p3971
- ISSN
0022-3751
- Publication type
Article
- DOI
10.1113/jphysiol.2010.194753