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心力衰竭伴射血分数保留的表观遗传重塑。

Epigenetic remodeling in heart failure with preserved ejection fraction.

机构信息

Center for Molecular Cardiology, University of Zurich, Zurich, Switzerland.

Department of Pharmacy, University of Pisa, Pisa, Italy.

出版信息

Curr Opin Cardiol. 2022 May 1;37(3):219-226. doi: 10.1097/HCO.0000000000000961. Epub 2022 Mar 11.

Abstract

PURPOSE OF REVIEW

In this review, we critically address the role of epigenetic processing and its therapeutic modulation in heart failure with preserved ejection fraction (HFpEF).

RECENT FINDINGS

HFpEF associates with a poor prognosis and the identification of novel molecular targets and therapeutic approaches are in high demand. Emerging evidence indicates a key involvement of epigenetic signals in the regulation of transcriptional programs underpinning features of HFpEF. The growing understanding of chromatin dynamics has led to the development of selective epigenetic drugs able to reset transcriptional changes thus delaying or preventing the progression toward HFpEF. Epigenetic information in the setting of HFpEF can be employed to: (i) dissect novel epigenetic networks and chromatin marks contributing to HFpEF; (ii) unveil circulating and cell-specific epigenetic biomarkers; (iii) build predictive models by using computational epigenetics and deep machine learning; (iv) develop new chromatin modifying drugs for personalized management of HFpEF.

SUMMARY

Acquired epigenetic signatures during the lifetime can contribute to derail molecular pathways involved in HFpEF. A scrutiny investigation of the individual epigenetic landscape will offer opportunities to develop personalized epigenetic biomarkers and therapies to fight HFpEF in the decades to come.

摘要

目的综述

在这篇综述中,我们批判性地探讨了表观遗传加工及其在射血分数保留心力衰竭(HFpEF)中的治疗调节作用。

最新发现

HFpEF 与预后不良有关,因此需要确定新的分子靶点和治疗方法。新出现的证据表明,表观遗传信号在调节 HFpEF 特征的转录程序中起着关键作用。对染色质动力学的认识不断加深,导致了选择性表观遗传药物的开发,这些药物能够重置转录变化,从而延缓或阻止向 HFpEF 的进展。HFpEF 中的表观遗传信息可用于:(i)剖析导致 HFpEF 的新的表观遗传网络和染色质标记;(ii)揭示循环和细胞特异性表观遗传生物标志物;(iii)通过计算表观遗传学和深度学习构建预测模型;(iv)开发新的染色质修饰药物,用于 HFpEF 的个体化管理。

总结

在一生中获得的表观遗传特征可能会导致参与 HFpEF 的分子途径脱轨。对个体表观遗传景观的仔细研究将为开发个性化的表观遗传生物标志物和治疗方法提供机会,以在未来几十年中对抗 HFpEF。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/66bf/9415220/2ed437169eae/cocar-37-219-g001.jpg

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