Superoxide signaling in perivascular adipose tissue promotes age-related artery stiffness.
Superoxide signaling in perivascular adipose tissue promotes age-related artery stiffness.
复制标题
DOI：
10.1111/acel.12196
复制
发表时间：
2014-06
期刊：
影响因子：
7.8
通讯作者：
Seals DR
中科院分区：
文献类型：
--
作者：
Fleenor BS;Eng JS;Sindler AL;Pham BT;Kloor JD;Seals DR
我们测试了这样的假设：主动脉血管周围脂肪组织（PVAT）内的超氧化物信号传导导致老年小鼠大弹性动脉僵硬。对年轻（4-6 个月）、老年（26-28 个月）和用 4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL)（一种超氧化物清除剂）处理的老年雄性 C57BL6/N 小鼠（1 mm 在饮用水中持续 3 周）进行了研究。与年轻人相比，老年人的大动脉僵硬度更大，通过主动脉脉搏波速度（aPWV，436±9 vs. 344±5 cm s-1）和内在机械测试（3821±427 vs. 1925±271 kPa）评估（均 P < 0.05）。过去的 TEMPOL 治疗逆转了动脉僵硬度的两种测量结果。老年主动脉 PVAT 超氧化物产生量更高（与 Y 相比，P < 0.05），并使用 TEMPOL 对其进行了标准化。与年轻人相比，老年对照组在 PVAT 条件培养基中具有更多的促炎蛋白（P < 0.05）。与年轻供体相比，接受年老PVAT移植的年轻受体小鼠8周具有更高的aPWV（409±7 vs. 342±8 cm s-1）和内在机械特性（3197±647 vs. 1889±520 kPa）（均P < 0.05），而在年老供体中补充TEMPOL后，这一现象被消除。与不存在PVAT 的旧培养的主动脉节段以及使用PVAT 和TEMPOL 的旧培养的主动脉节段相比，存在PVAT 的旧主动脉节段的组织培养具有更大的机械硬化（两者，P < 0.05）。此外，PVAT 衍生的超氧化物与动脉壁肥厚和随着衰老而增加的外膜 I 型胶原蛋白表达有关，而 TEMPOL 可以减弱这种作用。衰老或 TEMPOL 治疗不会影响血压。我们的研究结果为PVAT中与年龄相关的超氧化物产生和促炎蛋白增加提供了证据，并将PVAT中的超氧化物信号传导与大弹性动脉僵硬度直接联系起来。
We tested the hypothesis that superoxide signaling within aortic perivascular adipose tissue (PVAT) contributes to large elastic artery stiffening in old mice. Young (4–6 months), old (26–28 months), and old treated with 4-Hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl (TEMPOL), a superoxide scavenger (1 mm in drinking water for 3 weeks), male C57BL6/N mice were studied. Compared with young, old had greater large artery stiffness assessed by aortic pulse wave velocity (aPWV, 436 ± 9 vs. 344 ± 5 cm s-1) and intrinsic mechanical testing (3821 ± 427 vs. 1925 ± 271 kPa) (both P < 0.05). TEMPOL treatment in old reversed both measures of arterial stiffness. Aortic PVAT superoxide production was greater in old (P < 0.05 vs. Y), which was normalized with TEMPOL. Compared with young, old controls had greater pro-inflammatory proteins in PVAT-conditioned media (P < 0.05). Young recipient mice transplanted with PVAT from old compared with young donors for 8 weeks had greater aPWV (409 ± 7 vs. 342 ± 8 cm s-1) and intrinsic mechanical properties (3197 ± 647 vs. 1889 ± 520 kPa) (both P < 0.05), which was abolished with TEMPOL supplementation in old donors. Tissue-cultured aortic segments from old in the presence of PVAT had greater mechanical stiffening compared with old cultured in the absence of PVAT and old with PVAT and TEMPOL (both, P < 0.05). In addition, PVAT-derived superoxide was associated with arterial wall hypertrophy and greater adventitial collagen I expression with aging that was attenuated by TEMPOL. Aging or TEMPOL treatment did not affect blood pressure. Our findings provide evidence for greater age-related superoxide production and pro-inflammatory proteins in PVAT, and directly link superoxide signaling in PVAT to large elastic artery stiffness.
登录
查看更多内容
影响因子：
37.8
作者：
Mitchell GF;Hwang SJ;Vasan RS;Larson MG;Pencina MJ;Hamburg NM;Vita JA;Levy D;Benjamin EJ
通讯作者：
Benjamin EJ
影响因子：
37.8
作者：
Sutton-Tyrrell, K;Najjar, SS;Newman, A
通讯作者：
Newman, A
影响因子：
7.8
作者：
Sindler AL;Fleenor BS;Calvert JW;Marshall KD;Zigler ML;Lefer DJ;Seals DR
通讯作者：
Seals DR
影响因子：
7.8
作者：
Fleenor BS;Seals DR;Zigler ML;Sindler AL
通讯作者：
Sindler AL
影响因子：
3.7
作者：
Findeisen HM;Pearson KJ;Gizard F;Zhao Y;Qing H;Jones KL;Cohn D;Heywood EB;de Cabo R;Bruemmer D
通讯作者：
Bruemmer D