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他汀类药物对有早发心肌梗死病史的年轻患者中沉默调节蛋白1和内皮型一氧化氮合酶表达的影响。

Effect of statins on sirtuin 1 and endothelial nitric oxide synthase expression in young patients with a history of premature myocardial infarction.

作者信息

Yamaç Aylin Hatice, Kılıç Ülkan

机构信息

Department of Cardiology, Bezmialem Foundation University Faculty of Medicine, İstanbul, Turkey.

出版信息

Turk Kardiyol Dern Ars. 2018 Apr;46(3):205-215. doi: 10.5543/tkda.2018.32724.

DOI:10.5543/tkda.2018.32724
PMID:29664427
Abstract

OBJECTIVE

The present study was an investigation of the effect of statins on the expression of circulating sirtuin 1 (SIRT1) and endothelial nitric oxide synthase (eNOS) proteins, and on the distribution of single nucleotide polymorphisms (SNPs) of the SIRT1 gene in patients with a history of premature myocardial infarction (PMI).

METHODS

A total of 108 patients who had suffered from a premature ST-elevation myocardial infarction (STEMI) under the age of 45 years were enrolled in this study. While 79 patients had been taking statins since the index event, 29 patients had discontinued statin treatment after hospital discharge due to noncompliance or insufficient information about the importance of continuous statin therapy in post-MI patients. The control group consisted of 91 healthy patients without a previous cardiovascular event. The levels of SIRT1 and eNOS protein; oxidative stress markers, like total antioxidant status (TAS), total oxidant status (TOS), and the oxidative stress index (OSI); as well as the distribution of the SNPs rs7069102 and rs2273773 were measured and analyzed.

RESULTS

A significant increase in the SIRT1 level (p<0.001) and a significant decrease in the eNOS level (p=0.001) was observed in all genotypes and alleles for both SNPs in patients who received statin therapy compared with the control group. Both SNPs were distributed in a similar frequency in the 2 MI groups, irrespective of statin treatment.

CONCLUSION

Statins induce SIRT1 protein, which might have a cardioprotective role after PMI. In addition, the eNOS protein level was low in all of the MI patients, suggesting that impairment of eNOS expression is disease-specific without a causal link to SIRT1.

摘要

目的

本研究旨在调查他汀类药物对早发心肌梗死(PMI)患者循环中沉默调节蛋白1(SIRT1)和内皮型一氧化氮合酶(eNOS)蛋白表达的影响,以及对SIRT1基因单核苷酸多态性(SNP)分布的影响。

方法

本研究共纳入108例年龄在45岁以下的早发ST段抬高型心肌梗死(STEMI)患者。其中79例患者自首次发病后一直在服用他汀类药物,29例患者因不依从或对心肌梗死后患者持续他汀治疗重要性的信息不足,在出院后停止了他汀治疗。对照组由91例无心血管疾病史的健康患者组成。检测并分析SIRT1和eNOS蛋白水平;氧化应激标志物,如总抗氧化状态(TAS)、总氧化状态(TOS)和氧化应激指数(OSI);以及SNP rs7069102和rs2273773的分布情况。

结果

与对照组相比,接受他汀治疗的患者中,两种SNP的所有基因型和等位基因的SIRT1水平均显著升高(p<0.001),eNOS水平显著降低(p=0.001)。无论是否接受他汀治疗,两种SNP在两个心肌梗死组中的分布频率相似。

结论

他汀类药物可诱导SIRT1蛋白,这可能在PMI后具有心脏保护作用。此外,所有心肌梗死患者的eNOS蛋白水平均较低,这表明eNOS表达受损是疾病特异性的,与SIRT1无因果关系。

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