Department of Cardiology, Faculty of Health, Medicine and Life Sciences, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
CARIM School for Cardiovascular Diseases, Faculty of Health, Medicine and Life Sciences, Maastricht University, PO Box 616, 6200 MD Maastricht, The Netherlands.
Cardiovasc Res. 2018 May 1;114(6):782-793. doi: 10.1093/cvr/cvy049.
Half of all heart failure patients have preserved ejection fraction (HFpEF). Comorbidities associated with and contributing to HFpEF include obesity, diabetes and hypertension. Still, the underlying pathophysiological mechanisms of HFpEF are unknown. A preliminary consensus proposes that the multi-morbidity triggers a state of systemic, chronic low-grade inflammation, and microvascular dysfunction, causing reduced nitric oxide bioavailability to adjacent cardiomyocytes. As a result, the cardiomyocyte remodels its contractile elements and fails to relax properly, causing diastolic dysfunction, and eventually HFpEF. HFpEF is a complex syndrome for which currently no efficient therapies exist. This is notably due to the current one-size-fits-all therapy approach that ignores individual patient differences. MicroRNAs have been studied in relation to pathophysiological mechanisms and comorbidities underlying and contributing to HFpEF. As regulators of gene expression, microRNAs may contribute to the pathophysiology of HFpEF. In addition, secreted circulating microRNAs are potential biomarkers and as such, they could help stratify the HFpEF population and open new ways for individualized therapies. In this review, we provide an overview of the ever-expanding world of non-coding RNAs and their contribution to the molecular mechanisms underlying HFpEF. We propose prospects for microRNAs in stratifying the HFpEF population. MicroRNAs add a new level of complexity to the regulatory network controlling cardiac function and hence the understanding of gene regulation becomes a fundamental piece in solving the HFpEF puzzle.
一半的心衰患者射血分数保留（HFpEF）。与 HFpEF 相关并促成其发生的合并症包括肥胖、糖尿病和高血压。尽管如此，HFpEF 的潜在病理生理机制仍不清楚。初步共识提出，多种合并症引发全身性、慢性低度炎症和微血管功能障碍状态，导致相邻心肌细胞中一氧化氮生物利用度降低。结果，心肌细胞重塑其收缩成分，无法适当放松，导致舒张功能障碍，并最终导致 HFpEF。HFpEF 是一种复杂的综合征，目前尚无有效的治疗方法。这主要是由于目前一刀切的治疗方法忽略了个体患者的差异。miRNA 与 HFpEF 发病机制和促成其发生的合并症有关。作为基因表达的调节剂，miRNA 可能有助于 HFpEF 的发病机制。此外，分泌的循环 miRNA 是潜在的生物标志物，因此，它们可以帮助分层 HFpEF 人群，并为个体化治疗开辟新途径。在这篇综述中，我们概述了不断扩展的非编码 RNA 世界及其对 HFpEF 潜在分子机制的贡献。我们提出了 miRNA 在分层 HFpEF 人群中的应用前景。miRNA 为控制心脏功能的调控网络增加了一个新的复杂性水平，因此，对基因调控的理解成为解决 HFpEF 难题的一个基本部分。
