Parvan Reza, Rolim Natale, Gevaert Andreas B, Cataliotti Alessandro, van Craenenbroeck Emeline M, Adams Volker, Wisløff Ulrik, Silva Gustavo Jose Justo
Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo, Oslo, Norway.
Department of Circulation and Medical Imaging, Norwegian University of Science and Technology, Trondheim, Norway.
ESC Heart Fail. 2025 Aug;12(4):3028-3041. doi: 10.1002/ehf2.15324. Epub 2025 Jun 2.
Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome accounting for half of heart failure cases. Although natriuretic peptides are the most accepted and extensively used biomarkers for heart failure, their diagnostic accuracy for HFpEF remains debatable. Here, we aimed to identify a panel of circulating microRNAs (miRNAs) as potential novel biomarkers for diagnosis of HFpEF in a preclinical model, subsequently validated in human HFpEF patients.
In a female hypertension-induced HFpEF model [Dahl/Salt Sensitive (DSS) rats], circulating miRNA levels were screened in the plasma via real-time quantitative polymerase chain reaction. DSS rats exhibited HFpEF features as indicated by diastolic dysfunction and adverse cardiac remodelling when fed a high-salt (8%) diet (n = 11) compared with a low-salt (0.3%) diet (n = 15). A panel of four circulating miRNAs (rno-let-7b-5p, rno-let-7e-5p, rno-miR-21-5p and rno-miR-140-3p) were found significantly altered in the DSS plasma. Clinical performance of miRNA expression analysis was assessed in publicly available datasets of human heart failure patients, including assessment of discrimination of different categories of heart failure [GSE53437; control = 30, heart failure with reduced ejection fraction (HFrEF) = 41, HFpEF = 19] and gender differences (GSE104150; female = 6, male = 10). The miRNA panel significantly discriminated HFpEF patients from healthy individuals and HFrEF patients. We also found significant downregulation of let-7b-5p and miR-21-5p in females compared with males, regardless of health status.
A panel of four circulating miRNAs was differently expressed in female HFpEF rats and significantly discriminated HFpEF patients from healthy individuals and HFrEF patients. This cross-species and bench-to-bedside approach demonstrates the potential of miRNA-based panels for HFpEF diagnosis.
射血分数保留的心力衰竭（HFpEF）是一种复杂的综合征，占心力衰竭病例的一半。尽管利钠肽是心力衰竭最被认可和广泛使用的生物标志物，但其对HFpEF的诊断准确性仍存在争议。在此，我们旨在鉴定一组循环微小RNA（miRNA）作为在临床前模型中诊断HFpEF的潜在新型生物标志物，随后在人类HFpEF患者中进行验证。
在雌性高血压诱导的HFpEF模型[ Dahl/盐敏感（DSS）大鼠]中，通过实时定量聚合酶链反应筛选血浆中的循环miRNA水平。与低盐（0.3%）饮食（n = 15）相比，高盐（8%）饮食喂养的DSS大鼠（n = 11）出现舒张功能障碍和不良心脏重塑，表现出HFpEF特征。发现一组四种循环miRNA（rno-let-7b-5p、rno-let-7e-5p、rno-miR-21-5p和rno-miR-140-3p）在DSS血浆中显著改变。在公开可用的人类心力衰竭患者数据集中评估miRNA表达分析的临床性能，包括评估不同类型心力衰竭的鉴别[GSE53437；对照组 = 30，射血分数降低的心力衰竭（HFrEF）= 41，HFpEF = 19]和性别差异（GSE104150；女性 = 6，男性 = 10）。该miRNA组显著区分HFpEF患者与健康个体和HFrEF患者。我们还发现，无论健康状况如何，女性中let-7b-5p和miR-21-5p均显著下调。
一组四种循环miRNA在雌性HFpEF大鼠中表达不同，并显著区分HFpEF患者与健康个体和HFrEF患者。这种跨物种和从实验台到病床旁的方法证明了基于miRNA的组在HFpEF诊断中的潜力。
