(-)-Epicatechin induced reversal of endothelial cell aging and improved vascular function: underlying mechanisms.
(-)-Epicatechin induced reversal of endothelial cell aging and improved vascular function: underlying mechanisms.
复制标题
（ - ） - 上皮细胞衰老和改善血管功能的逆转：潜在的机制。
DOI：
10.1039/c8fo00483h
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发表时间：
2018-09-19
期刊：
影响因子：
6.1
通讯作者：
Villarreal FJ
中科院分区：
文献类型：
--
作者：
Ramirez-Sanchez I ;Mansour C ;Navarrete-Yañez V ;Ayala-Hernandez M ;Guevara G ;Castillo C ;Loredo M ;Bustamante M ;Ceballos G ;Villarreal FJ
食用富含（−）-表儿茶素的可可制品与降低心血管风险和改善血管功能有关。然而，很少有人知道（-）-表儿茶素对老化内皮细胞的影响。为了表征（-）-表儿茶素对老化内皮的健康恢复作用并确定潜在的机制，我们使用了高传代次数（即老化）的牛冠状动脉内皮细胞和3和18月龄大鼠的动脉。我们评估了细胞衰老（β-半乳糖苷酶）、通过内皮一氧化氮合酶途径产生的一氧化氮（NO）、线粒体相关终点、柠檬酸合酶活性和血管舒张。细胞用水或（-）-epicate-chin（1 μM）处理48 h，大鼠口服水或（-）-epicatechin（1 mg kg-1 day-1）15天。衰老相关的β-半乳糖苷酶水平在衰老细胞中增加了一倍，而用（-）-epicate-chin处理的细胞仅增加了约40%。随着年龄的增长，细胞中的NO水平下降了约33%，（-）-epicate-chin使其正常化。内皮一氧化氮合酶磷酸化水平与这些结果相一致。衰老增加了总蛋白质和合成酶乙酰化水平，（−）-表儿茶素通过刺激沉默调节蛋白-1与合成酶的结合，使它们部分恢复到年轻细胞的水平。线粒体的磷酸化sirtuin-1、丝裂素、氧化磷酸化复合物和转录因子随着年龄的增长减少了约40%，并被（−）-表儿茶素恢复。（−）-表儿茶素增强乙酰胆碱诱导的老年主动脉血管舒张，刺激NO水平，同时降低血压。总之，（−）-表儿茶素逆转内皮细胞衰老，恢复血管功能的关键控制元素。这些作用可以部分解释可可消费对心脏和血管疾病发病率有益的流行病学证据。
The consumption of cocoa products rich in (−)-epicatechin is associated with reduced cardiovascular risk and improved vascular function. However, little is known about (−)-epicatechin’s effects on aged endothelium. In order to characterize the health restoring effects of (−)-epicatechin on aged endothelium and identify the underlying mechanisms, we utilized high passage number (i.e. aged) bovine coronary artery endothelial cells and aortas of 3 and 18 month old rats. We evaluated cell senescence (β-galactosidase), nitric oxide (NO) production through the endothelial nitric oxide synthase pathway, mitochondria related endpoints, citrate synthase activity and vascular relaxation. Cells were treated with water or (−)-epicate-chin (1 μM) for 48 h and rats orally with either water or (−)-epicatechin (1 mg kg−1 day−1) for 15 days. Senescence associated β-galactosidase levels doubled in aged cells while those treated with (−)-epicate-chin only evidenced an ~40% increase. NO levels in cells decreased by ~33% with aging and (−)-epicate-chin normalized them. Endothelial nitric oxide synthase phosphorylation levels paralleled these results. Aging increased total protein and synthase acetylation levels and (−)-epicatechin partially restored them to those of young cells by stimulating sirtuin-1 binding to the synthase. Phosphorylated sirtuin-1, mitofilin, oxidative phosphorylation complexes and transcriptional factor for mitochondria were reduced by ~40% with aging and were restored by (−)-epicatechin. (−)-Epicatechin enhanced acetylcholine induced aged aorta vasodilation and stimulated NO levels while reducing blood pressure. In conclusion, (−)-epicatechin reverses endothelial cell aging and restores key control elements of vascular function. These actions may partly explain the epidemiological evidence for the beneficial effects of cocoa consumption on the incidence of cardiac and vascular diseases.
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DOI：
10.18632/aging.101068
发表时间：
2016-10-15
期刊：
Aging
影响因子：
--
作者：
Kitada M;Ogura Y;Koya D
通讯作者：
Koya D
DOI：
10.1136/heartjnl-2014-307050
发表时间：
2015-08
期刊：
Heart (British Cardiac Society)
影响因子：
--
作者：
Kwok CS;Boekholdt SM;Lentjes MA;Loke YK;Luben RN;Yeong JK;Wareham NJ;Myint PK;Khaw KT
通讯作者：
Khaw KT
影响因子：
8.3
作者：
Kapil, Vikas;Milsom, Alexandra B.;Ahluwalia, Amrita
通讯作者：
Ahluwalia, Amrita
DOI：
10.1016/j.bbrc.2010.01.080
发表时间：
2010-02-26
影响因子：
3.1
作者：
Arunachalam, Gnanapragasam;Yao, Hongwei;Sundar, Isaac K.;Caito, Samuel;Rahman, Irfan
通讯作者：
Rahman, Irfan
影响因子：
25
作者：
Brickman AM;Khan UA;Provenzano FA;Yeung LK;Suzuki W;Schroeter H;Wall M;Sloan RP;Small SA
通讯作者：
Small SA