MicroRNA changes in human arterial endothelial cells with senescence: relation to apoptosis, eNOS and inflammation.
MicroRNA changes in human arterial endothelial cells with senescence: relation to apoptosis, eNOS and inflammation.
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DOI：
10.1016/j.exger.2011.10.004
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发表时间：
2012-01
影响因子：
3.9
通讯作者：
Seals, Douglas R.
中科院分区：
文献类型：
--
作者：
Rippe, Catarina;Blimline, Mark;Magerko, Katherine A.;Lawson, Brooke R.;LaRocca, Thomas J.;Donato, Anthony J.;Seals, Douglas R.
内皮细胞中的衰老表型与增加的细胞凋亡、减少的内皮一氧化氮合酶（eNOS）和炎症相关，这与人类的动脉功能障碍和疾病有关。我们检验了microRNA的变化与人主动脉内皮细胞（HAEC）衰老表型相关的假设。与早代HAEC相比，晚代HAEC的增殖率降低，衰老相关β-半乳糖苷酶和肿瘤抑制因子p16 INK 4a的染色增加。晚期传代衰老HAEC的增殖刺激/凋亡抑制miR-21、miR-214和miR-92的表达降低，而肿瘤抑制因子和凋亡标志物的表达增加。在衰老的HAEC中，eNOS抑制性miR-221和miR-222增加，eNOS蛋白和eNOS活化（丝氨酸1177处的磷酸化）降低。在衰老的HAEC中，抑制miR-133 a的小窝蛋白-1减少，而eNOS活性的负调节因子小窝蛋白-1升高。抑制炎症的miR-126减少，刺激炎症的miR-125 b增加，而衰老的HAEC中的炎症蛋白更大。衰老动脉内皮细胞表型的发展特征在于细胞增殖减少、细胞凋亡和炎症增强以及eNOS减少，这与与这些过程的调节相关的miRNA的变化有关。我们的研究结果支持了miRNAs在动脉内皮细胞衰老中发挥关键作用的假设。
A senescent phenotype in endothelial cells is associated with increased apoptosis, reduced endothelial nitric oxide synthase (eNOS) and inflammation, which are implicated in arterial dysfunction and disease in humans. We tested the hypothesis that changes in microRNAs are associated with a senescent phenotype in human aortic endothelial cells (HAEC). Compared with early-passage HAEC, late-passage HAEC had a reduced proliferation rate and increased staining for senescence-associated beta-galactosidase and the tumor suppressor p16INK4a. Late-passage senescent HAEC had reduced expression of proliferation-stimulating/apoptosis-suppressing miR-21, miR-214 and miR-92 and increased expression of tumor suppressors and apoptotic markers. eNOS-suppressing miR-221 and miR-222 were increased and eNOS protein and eNOS activation (phosphorylation at serine1177) were lower in senescent HAEC. Caveolin-1 inhibiting miR-133a was reduced and caveolin-1, a negative regulator of eNOS activity, was elevated in senescent HAEC. Inflammation-repressing miR-126 was reduced and inflammation–stimulating miR-125b was increased, whereas inflammatory proteins were greater in senescent HAEC. Development of a senescent arterial endothelial cell phenotype featuring reduced cell proliferation, enhanced apoptosis and inflammation and reduced eNOS is associated with changes in miRNAs linked to the regulation of these processes. Our results support the hypothesis that miRNAs could play a critical role in arterial endothelial cell senescence.
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影响因子：
4.6
作者：
Chan, Lai-Sheung;Yue, Patrick Ying-Kit;Wong, Ricky Ngok-Shun
通讯作者：
Wong, Ricky Ngok-Shun
DOI：
10.1146/annurev-pathol-121808-102144
发表时间：
2010
期刊：
Annual review of pathology
影响因子：
--
作者：
Coppé JP;Desprez PY;Krtolica A;Campisi J
通讯作者：
Campisi J
DOI：
10.1073/pnas.92.20.9363
发表时间：
1995-09-26
影响因子：
11.1
作者：
DIMRI, GP;LEE, XH;CAMPISI, J
通讯作者：
CAMPISI, J
影响因子：
4.8
作者：
Ju, H;Zou, R;Venema, RC
通讯作者：
Venema, RC
影响因子：
7.8
作者：
Hackl M;Brunner S;Fortschegger K;Schreiner C;Micutkova L;Mück C;Laschober GT;Lepperdinger G;Sampson N;Berger P;Herndler-Brandstetter D;Wieser M;Kühnel H;Strasser A;Rinnerthaler M;Breitenbach M;Mildner M;Eckhart L;Tschachler E;Trost A;Bauer JW;Papak C;Trajanoski Z;Scheideler M;Grillari-Voglauer R;Grubeck-Loebenstein B;Jansen-Dürr P;Grillari J
通讯作者：
Grillari J