Senescence as a novel mechanism involved in β-adrenergic receptor mediated cardiac hypertrophy.
Senescence as a novel mechanism involved in β-adrenergic receptor mediated cardiac hypertrophy.
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衰老作为β-肾上腺素能受体介导的心脏肥大的一种新机制
DOI：
10.1371/journal.pone.0182668
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Xue L
中科院分区：
文献类型：
--
作者：
Sun R;Zhu B;Xiong K;Sun Y;Shi D;Chen L;Zhang Y;Li Z;Xue L
病理性心肌肥厚过去常通过生物力学、牵拉敏感或神经体液机制来阐明。然而，一系列的线索表明，肥大过程模拟了衰老程序。然而，还需要寻找更多的证据。为了验证这一假说，并验证心脏衰老是否是异丙肾上腺素诱导的肥大的新机制，2月龄雄性SD大鼠皮下注射异丙肾上腺素(0.25 mg/kg/d，连续7天)。在心肌肥厚模型中检测衰老的关键特征(衰老相关的β-半乳糖苷酶活性、脂褐素、细胞周期蛋白依赖性激酶抑制物的表达)。在心肌肥厚的过程中，发现了类似衰老的表型，如衰老相关的β半乳糖苷酶活性增加，脂褐素积聚，以及高水平的细胞周期蛋白依赖性激酶抑制物(如p16、p19、p21和p53)。在异丙肾上腺素处理的心肌细胞中，心脏特异性转录因子GATA4也增加。我们进一步发现，抗衰老化合物白藜芦醇可以剂量依赖的方式抑制心肌肥厚。我们的结果首次表明心脏衰老参与了异丙肾上腺素诱导的病理性心肌肥大过程。
Pathological cardiac hypertrophy used to be elucidated by biomechanical, stretch-sensitive or neurohumoral mechanisms. However, a series of hints have indicated that hypertrophy process simulates senescence program. However, further evidence need to be pursued. To verify this hypothesis and examine whether cardiac senescence is a novel mechanism of hypertrophy induced by isoproterenol, 2-month-old male Sprague Dawley rats were subjected to isoproterenol infusion (0.25mg/kg/day) for 7 days by subcutaneous injection). Key characteristics of senescence (senescence-associated β-galactosidase activity, lipofuscin, expression of cyclin-dependent kinase inhibitors) were examined in cardiac hypertrophy model. Senescence-like phenotype, such as increased senescence-associated β-galactosidase activity, accumulation of lipofuscin and high levels of cyclin-dependent kinase inhibitors (e.g. p16, p19, p21 and p53) was found along the process of cardiac hypertrophy. Cardiac-specific transcription factor GATA4 increased in isoproterenol-treated cardiomyocytes as well. We further found that myocardial hypertrophy could be inhibited by resveratrol, an anti-aging compound, in a dose-dependent manner. Our results showed for the first time that cardiac senescence is involved in the process of pathological cardiac hypertrophy induced by isoproterenol.
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DOI：
10.18632/aging.100273
发表时间：
2011-02
期刊：
Aging
影响因子：
--
作者：
Anisimov VN;Berstein LM;Popovich IG;Zabezhinski MA;Egormin PA;Piskunova TS;Semenchenko AV;Tyndyk ML;Yurova MN;Kovalenko IG;Poroshina TE
通讯作者：
Poroshina TE
影响因子：
37.8
作者：
Inuzuka, Yasutaka;Okuda, Junji;Shioi, Tetsuo
通讯作者：
Shioi, Tetsuo
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：
6
作者：
Kajstura, J;Pertoldi, B;Anversa, P
通讯作者：
Anversa, P
影响因子：
5.3
作者：
Hernández JS;Barreto-Torres G;Kuznetsov AV;Khuchua Z;Javadov S
通讯作者：
Javadov S