Arterial stiffening with ageing is associated with transforming growth factor-β1-related changes in adventitial collagen: reversal by aerobic exercise
Arterial stiffening with ageing is associated with transforming growth factor-β1-related changes in adventitial collagen: reversal by aerobic exercise
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DOI：
10.1113/jphysiol.2010.194753
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发表时间：
2010-10-15
影响因子：
5.5
通讯作者：
Seals, Douglas R.
中科院分区：
文献类型：
--
作者：
Fleenor, Bradley S.;Marshall, Kurt D.;Seals, Douglas R.
我们检验了这样一个假设，即颈动脉硬化与年龄有关，与转化生长因子-β 1（TGF-β 1）相关的外膜胶原蛋白增加和中膜弹性蛋白减少有关，这将通过自愿有氧运动逆转。老年人的离体颈动脉刚度增量更大，（29-32个月，n = 11）与年轻（4-7个月，n = 8）笼内对照B6 D2 F1小鼠（8.84 +/- 1.80 vs. 4.54 +/- 1.18 Au，P < 0.05），并与外膜中胶原蛋白I和III以及TGF-β 1蛋白表达的选择性增加相关（P < 0.05），与平滑肌α-肌动蛋白（SM α A）（肌成纤维细胞表型）的增加有关（P < 0.05）。在培养的外膜成纤维细胞中，TGF-β 1诱导超氧化物和I型胶原蛋白的增加（P < 0.05），而超氧化物歧化酶Tempol可抑制该作用。随着年龄的增长，内侧弹性蛋白减少，伴随着合成弹性蛋白酶赖氨酰氧化酶的减少，弹性蛋白降解酶基质金属蛋白酶2的增加。随着年龄的增长，纤连蛋白没有变化，但钙化略有增加（P < 0.05）。通过10-14周的适度自愿轮跑（1.13 +/- 0.29 km天-1），老年小鼠增加的增量刚度完全逆转（3.98 +/- 0.34 Au，n = 5），而更大的自愿轮跑（10.62 +/- 0.49 km天-1）对年轻小鼠没有影响。老年小鼠通过车轮跑步改善颈动脉僵硬与胶原蛋白I和III以及TGF-β 1的减少、肌成纤维细胞表型的部分逆转（SM α A减少）和钙化减少（与老年对照组相比，所有P < 0.05）相关，而弹性蛋白及其调节酶不受影响。外膜TGF-β 1相关的氧化应激可能在胶原沉积和大弹性动脉硬化中起关键作用，并与自愿有氧运动的有效作用有关。
We tested the hypothesis that carotid artery stiffening with ageing is associated with transforming growth factor-beta 1 (TGF-beta 1)-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-beta 1 protein expression in the adventitia (P < 0.05), related to an increase in smooth muscle alpha-actin (SM alpha A) (myofibroblast phenotype) (P < 0.05). In cultured adventitial fibroblasts, TGF-beta 1 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-beta 1, partial reversal of the myofibroblast phenotype (reduced SM alpha A) and reduced calcification (all P < 0.05 vs. old controls), whereas elastin and its modulating enzymes were unaffected. Adventitial TGF-beta 1-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.