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在西弗吉尼亚州人群中,针对心肌梗死患者开发一组生物标志物和 miRNA,以制定心力衰竭的早期干预策略。

Developing a panel of biomarkers and miRNA in patients with myocardial infarction for early intervention strategies of heart failure in West Virginian population.

机构信息

Department of Internal Medicine, Marshall University Joan C Edwards School of Medicine, Huntington, WV, United States of America.

Division of Cardiology, Department of Internal Medicine, Marshall University Joan C Edwards School of Medicine, Huntington, WV, United States of America.

出版信息

PLoS One. 2018 Oct 24;13(10):e0205329. doi: 10.1371/journal.pone.0205329. eCollection 2018.

Abstract

BACKGROUND

Myocardial infarction is the most common cause of heart failure. MI has been intricately linked to ventricular remodeling, subsequently leading to the reduction in the cardiac ejection fraction causing HF. The cumulative line of evidence suggests an important role of several biomarkers in modulating the cardiac vasculature, further contributing towards the progression of post-MI complications. Studies have demonstrated, yet not fully established, that an important biomarker, IL-10, has a causal relationship with MI and associated cardiac dysfunction.

HYPOTHESIS

This study aims to establish the role of IL-10 as a prognostic marker for the cardiovascular outcomes and to develop a panel of biomarkers and circulating miRNAs that could potentially result in the early detection of HF resulting from MI, allowing for early intervention strategies.

METHODS AND RESULTS

Blood was withdrawn and echocardiography assessment was performed on a total of 43 patients that were enrolled, within 24 hours of the incidence of MI. Patients were divided in three main groups, based on the ejection fraction measurement from echocardiography: control (n = 14), MI with normal EF (MI+NEF, n = 13) and MI with low EF (MI+LEF, n = 16). Our results showed that TGFβ-1, TNF-α, IL-6 and MMP-9 were upregulated significantly in MI+NEF group and more so in MI+LEF group, as compared to control group (p<0.01). The circulating levels of miR-34a, miR-208b and miR-126 were positively correlated and showed elevated levels in the MI+NEF group, even higher in MI+LEF group, while levels of miR-24 and miR-29a were reduced in MI+NEF, and much lower in MI+LEF, as compared to the control group (p<0.01). Our results also demonstrated a direct correlation of IL-10 with the ejection fraction in patients with MI: IL-10 was elevated in MI+NEF group, however, the levels were significantly low in MI+LEF group suggesting an important role of IL-10 in predicting heart failure. Importantly, our study confirmed the correlation of IL-10 with EF by our follow-up echocardiography assessment that was performed 2 months after the incidence of MI.

CONCLUSION

Our results support the clinical application of these serum biomarkers to develop a panel for appropriate prognosis and management of adverse cardiac remodeling and development of heart failure post-myocardial infarction.

摘要

背景

心肌梗死是心力衰竭最常见的病因。MI 与心室重构密切相关,随后导致心脏射血分数降低,导致 HF。越来越多的证据表明,几种生物标志物在调节心脏血管方面起着重要作用,进一步导致 MI 后并发症的进展。研究表明,但尚未完全确定,一种重要的生物标志物 IL-10 与 MI 和相关的心脏功能障碍有因果关系。

假设

本研究旨在确定 IL-10 作为心血管结局的预后标志物的作用,并开发一组生物标志物和循环 miRNA,这些标志物可能会导致 MI 引起的 HF 的早期检测,从而实现早期干预策略。

方法和结果

总共对 43 名在 MI 发生后 24 小时内入组的患者进行了采血和超声心动图评估。根据超声心动图测量的射血分数,患者分为三组:对照组(n = 14)、MI 伴正常 EF(MI+NEF,n = 13)和 MI 伴低 EF(MI+LEF,n = 16)。我们的结果表明,TGFβ-1、TNF-α、IL-6 和 MMP-9 在 MI+NEF 组中显著上调,在 MI+LEF 组中上调更为明显,与对照组相比(p<0.01)。miR-34a、miR-208b 和 miR-126 的循环水平呈正相关,在 MI+NEF 组中升高,在 MI+LEF 组中升高更为明显,而 miR-24 和 miR-29a 在 MI+NEF 中降低,在 MI+LEF 中降低更为明显,与对照组相比(p<0.01)。我们的结果还表明,IL-10 与 MI 患者的射血分数之间存在直接相关性:IL-10 在 MI+NEF 组中升高,但在 MI+LEF 组中显著降低,表明 IL-10 在预测心力衰竭方面起着重要作用。重要的是,我们的研究通过我们在 MI 发生后 2 个月进行的后续超声心动图评估证实了 IL-10 与 EF 的相关性。

结论

我们的结果支持将这些血清生物标志物应用于临床,以开发用于适当预后和管理不良心脏重构以及 MI 后心力衰竭发展的面板。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3567/6200226/f92014817e7a/pone.0205329.g001.jpg

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