表观遗传药物:治疗心力衰竭的新领域

K. Aitbaev, I. Murkamilov, Z. Murkamilova, V. V. Fomin, I. Kudaibergenova, T. F. Yusupova, F. Yusupov
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引用次数: 0

摘要

揭开基因组灵活性的秘密不仅促进了这一领域研究的发展,还推动了人类疾病新疗法的开发。由于对染色质(DNA/组蛋白复合物)和非编码 RNA(ncRNA)的生物学有了更深入的了解,开发出了能够调节与心血管疾病相关的转录程序的表观遗传(epi)制剂。表观遗传机制已被证明是左心室肥大、纤维化、心肌细胞凋亡和微血管功能障碍等多种病理过程的基础。针对表观遗传信号可能是一种很有前景的方法,尤其是对于射血分数保留型心力衰竭(HFpEF)患者,因为这些患者的预后仍然很差,而且还没有有效的治疗方法。在这种情况下,表观遗传学可用于开发个体化治疗方法,为个性化医疗铺平道路。虽然表观遗传学药物的益处越来越受到关注,但用于临床实践的表观遗传学化合物数量仍然很少,这表明有必要开发更具选择性的表观遗传学药物。在这篇综述中,我们列出了一系列治疗心血管疾病的新型表观遗传药物,主要集中在高频心衰方面。这些药物的治疗效果归功于对三种主要表观遗传机制中至少一种机制的影响:DNA甲基化、组蛋白修饰和非编码RNA。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Epigenetic drugs: a new frontier in the treatment of heart failure
Uncovering the secrets of genome flexibility not only contributed to the development of research in this area, but also served as an impetus for the development of new treatments for human diseases. A better understanding of the biology of chromatin (DNA/histone complexes) and non-coding RNAs (ncRNAs) has enabled the development of epigenetic (epi) preparations capable of modulating transcriptional programs associated with cardiovascular disease. This is especially true in heart failure, where epigenetic mechanisms have been shown to underlie the development of several pathological processes such as left ventricular hypertrophy, fibrosis, cardiomyocyte apoptosis, and microvascular dysfunction. Targeting epigenetic signals may represent a promising approach, especially in patients with heart failure with preserved ejection fraction (HFpEF), where the prognosis remains poor and effective treatments are not yet available. Under these conditions, epigenetics can be used to develop individualized therapeutic approaches, paving the way for personalized medicine. Although the beneficial effects of epi-drugs are gaining more attention, the number of epigenetic compounds used in clinical practice remains low, suggesting the need to develop more selective epi-drugs. In this review, we present a list of new promising epi-drugs for the treatment of cardiovascular diseases, with a focus mainly on HFpEF. The therapeutic effect of these drugs is due to the impact on at least one of the three main epigenetic mechanisms: DNA methylation, histone modification, and non-coding RNA.
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