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RNA疗法在治疗心血管疾病中的潜力。

The Potential of RNA Therapeutics in Treating Cardiovascular Disease.

作者信息

Mainkar Gayatri, Ghiringhelli Matteo, Zangi Lior

机构信息

Icahn School of Medicine at Mount Sinai, Cardiovascular Research Institute, New York, NY, 10029, USA.

Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, 10029, USA.

出版信息

Drugs. 2025 May;85(5):659-676. doi: 10.1007/s40265-025-02173-1. Epub 2025 Apr 2.

Abstract

Despite significant advances in cardiology over the past few decades, cardiovascular diseases (CVDs) remain the leading cause of global mortality and morbidity. This underscores the need for novel therapeutic interventions that go beyond symptom management to address the underlying causal mechanisms of CVDs. RNA-based therapeutics represent a new class of drugs capable of regulating specific genetic and molecular pathways, positioning them as strong candidates for targeting the root causes of a wide range of diseases. Moreover, owing to the vast diversity in RNA form and function, these molecules can be utilized to induce changes at different levels of gene expression regulation, making them suitable for a broad array of medical applications, even within a single disease context. Several RNA-based therapies are currently being investigated for their potential to address various CVD pathologies. These include treatments aimed at promoting cardiac revascularization and regeneration, preventing cardiomyocyte apoptosis, reducing harmful circulating cholesterols and fats, lowering blood pressure, reversing cardiac fibrosis and remodeling, and correcting the genetic basis of inherited CVDs. In this review, we discuss the current landscape of RNA therapeutics for CVDs, with an emphasis on their classifications, modes of action, advancements in delivery strategies and considerations for their implementation, as well as CVD targets with proven therapeutic potential.

摘要

尽管在过去几十年中心脏病学取得了重大进展,但心血管疾病(CVDs)仍然是全球死亡率和发病率的主要原因。这凸显了对新型治疗干预措施的需求,这些干预措施不仅要管理症状,还要解决CVDs的潜在因果机制。基于RNA的疗法代表了一类新型药物,能够调节特定的基因和分子途径,使其成为针对多种疾病根本原因的有力候选药物。此外,由于RNA形式和功能的巨大多样性,这些分子可用于在基因表达调控的不同水平上诱导变化,使其适用于广泛的医学应用,甚至在单一疾病背景下也是如此。目前正在研究几种基于RNA的疗法治疗各种CVD病理的潜力。这些治疗方法包括旨在促进心脏血管再生和修复、预防心肌细胞凋亡、降低有害循环胆固醇和脂肪、降低血压、逆转心脏纤维化和重塑,以及纠正遗传性CVDs的遗传基础。在这篇综述中,我们讨论了用于CVDs的RNA疗法的现状,重点介绍了它们的分类、作用方式、递送策略的进展以及实施时的考虑因素,以及具有已证实治疗潜力的CVD靶点。

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