Deficiency of senescence marker protein 30 exacerbates angiotensin II-induced cardiac remodelling
Deficiency of senescence marker protein 30 exacerbates angiotensin II-induced cardiac remodelling
复制标题
衰老标记蛋白 30 的缺乏会加剧血管紧张素 II 诱导的心脏重塑
DOI：
10.1093/cvr/cvt122
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发表时间：
2013
影响因子：
10.8
通讯作者：
Takeishi Y
中科院分区：
文献类型：
--
作者：
Misaka T;Suzuki S;Miyata M;Kobayashi A;Shishido T;Ishigami A;Saitoh S;Hirose M;Kubota I;Takeishi Y
目的老龄化是包括心力衰竭在内的心血管疾病的重要危险因素。衰老标志蛋白30（SMP 30）最初被认为是一种重要的衰老标志蛋白，目前被认为是多种器官中的一种新的抗衰老因子。然而，SMP 30在心脏中的作用以前没有被探索过。在这项研究中，我们的目的是阐明SMP 30对心脏remodeling.Methods和resultsSMP 30基因敲除（KO）小鼠和野生型（WT）小鼠的功能作用进行了连续血管紧张素II（Ang II）输注。14天后，SMP 30-KO小鼠的心脏肥大和心肌纤维化程度显著高于WT小鼠。超声心动图显示，与WT小鼠相比，SMP 30-KO小鼠具有更严重的收缩和舒张功能抑制，左心室扩张。与烟酰胺腺嘌呤二核苷酸磷酸氧化酶的活化相关的活性氧簇的产生在SMP 30-KO小鼠中比在WT小鼠中更大。与WT小鼠相比，SMP 30-KO小鼠中脱氧核苷酸转移酶介导的dUTP缺口末端标记阳性细胞核的数量显著增加，caspase-3活化，Bax/Bcl-2比率增加，c-Jun N-末端激酶磷酸化。此外，衰老相关的β-半乳糖苷酶阳性细胞的数量显着增加，通过上调p21基因表达在SMP 30-KO小鼠与WT mice.ConclusionThis研究表明，第一个证据表明，缺乏SMP 30加剧Ang II诱导的心脏肥大，功能障碍，和重塑，提示SMP 30在心脏重塑中具有心脏保护作用，具有响应于Ang II的抗氧化和抗凋亡作用。
AimsAgeing is an important risk factor of cardiovascular diseases including heart failure. Senescence marker protein 30 (SMP30), which was originally identified as an important ageing marker protein, is assumed to act as a novel anti-ageing factor in various organs. However, the role of SMP30 in the heart has not been previously explored. In this study, our aim was to elucidate the functional role of SMP30 on cardiac remodelling.Methods and resultsSMP30 knockout (KO) mice and wild-type (WT) mice were subjected to continuous angiotensin II (Ang II) infusion. After 14 days, the extent of cardiac hypertrophy and myocardial fibrosis was significantly higher in SMP30-KO mice than in WT mice. Echocardiography revealed that SMP30-KO mice had more severely depressed systolic and diastolic function with left ventricular dilatation compared with WT mice. Generation of reactive oxygen species related with activation of nicotinamide adenine dinucleotide phosphate-oxidase was greater in SMP30-KO mice than in WT mice. The number of deoxynucleotidyl transferase-mediated dUTP nick end-labelling positive nuclei was markedly increased in SMP30-KO mice with activation of caspase-3, increases in the Bax to Bcl-2 ratio and phosphorylation of c-Jun N-terminal kinase compared with WT mice. Furthermore, the number of senescence-associated β-galactosidase-positive cells was significantly increased via up-regulation of p21 gene expression in SMP30-KO mice compared with WT mice.ConclusionThis study demonstrated the first evidence that deficiency of SMP30 exacerbates Ang II-induced cardiac hypertrophy, dysfunction, and remodelling, suggesting that SMP30 has a cardio-protective role in cardiac remodelling with anti-oxidative and anti-apoptotic effects in response to Ang II.