Endothelial Cell Senescence Increases Traction Forces due to Age-Associated Changes in the Glycocalyx and SIRT1.
Endothelial Cell Senescence Increases Traction Forces due to Age-Associated Changes in the Glycocalyx and SIRT1.
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DOI：
10.1007/s12195-014-0371-6
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发表时间：
2015-03-01
影响因子：
2.8
通讯作者：
Truskey, George A.
中科院分区：
文献类型：
--
作者：
Cheung, Tracy M.;Yan, Jessica B.;Fu, Justin J.;Huang, Jianyong;Yuan, Fan;Truskey, George A.
血管内皮细胞(EC)老化和衰老是动脉粥样硬化形成和心血管疾病发展的关键事件。与年龄相关的局部血管机械环境的变化也与动脉粥样硬化有关。然而，细胞衰老对细胞产生的机械力的影响程度尚不清楚。在这项研究中，我们试图确定EC衰老是否通过与年龄相关的糖萼和抗氧化剂调节因子脱乙酰基酶Sirtuin1(SIRT1)的变化来增加牵引力，SIRT1在衰老过程中下调。在经历更多群体倍增的细胞中，牵引力更高，牵引力的变化与肌动蛋白定位的改变有关。年龄较大的细胞肌动蛋白细丝厚度也增加。去除年轻内皮细胞中的硫酸肝素可增加牵引力和肌动蛋白细丝厚度，而通过血管生成素-1处理的老年内皮细胞表面添加硫酸肝素则有相反的作用。抑制SIRT1对年轻细胞的牵引力或肌动蛋白组织无显著影响，但激活SIRT1确实减少了牵引力，增加了老年内皮细胞的外周肌动蛋白。这些结果表明，EC衰老通过改变SIRT1和糖萼来增加牵引力和改变肌动蛋白的定位。
Endothelial cell (EC) aging and senescence are key events in atherogenesis and cardiovascular disease development. Age-associated changes in the local mechanical environment of blood vessels have also been linked to atherosclerosis. However, the extent to which cell senescence affects mechanical forces generated by the cell is unclear. In this study, we sought to determine whether EC senescence increases traction forces through age-associated changes in the glycocalyx and antioxidant regulator deacetylase Sirtuin1 (SIRT1), which is downregulated during aging. Traction forces were higher in cells that had undergone more population doublings and changes in traction force were associated with altered actin localization. Older cells also had increased actin filament thickness. Depletion of heparan sulfate in young ECs elevated traction forces and actin filament thickness, while addition of heparan sulfate to the surface of aged ECs by treatment with angiopoietin-1 had the opposite effect. While inhibition of SIRT1 had no significant effect on traction forces or actin organization for young cells, activation of SIRT1 did reduce traction forces and increase peripheral actin in aged ECs. These results show that EC senescence increases traction forces and alters actin localization through changes to SIRT1 and the glycocalyx.
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影响因子：
64.5
作者：
Choquet, D;Felsenfeld, DP;Sheetz, MP
通讯作者：
Sheetz, MP
DOI：
10.1083/jcb.134.3.783
发表时间：
1996-08
期刊：
The Journal of cell biology
影响因子：
--
作者：
Garfinkel S;Hu X;Prudovsky IA;McMahon GA;Kapnik EM;McDowell SD;Maciag T
通讯作者：
Maciag T
影响因子：
2.7
作者：
Erusalimsky, Jorge D.;Skene, Chris
通讯作者：
Skene, Chris
影响因子：
2.8
作者：
Giantsos-Adams, Kristina M.;Koo, Andrew Jia-An;Song, Sukhyun;Sakai, Jiro;Sankaran, Jagadish;Shin, Jennifer H.;Garcia-Cardena, Guillermo;Dewey, C. Forbes, Jr.
通讯作者：
Dewey, C. Forbes, Jr.
DOI：
10.1152/ajpheart.00182.2012
发表时间：
2012-12-01
影响因子：
4.8
作者：
Cheung, Tracy M.;Ganatra, Mansi P.;Truskey, George A.
通讯作者：
Truskey, George A.