Researchers from IRBLleida are taking part in a European study that identifies new molecular mechanisms involved in the progression of heart failure

A European multicentre study involving the Institute for Biomedical Research in Lleida (IRBLleida) has identified three microRNAs circulating in the blood that are associated with the development of heart failure, one of the leading causes of death and hospitalisation worldwide. The findings have recently been published in the scientific journal European Journal of Internal Medicine.

"These results reveal the molecular mechanisms underlying the progression of heart failure and open the door to new therapeutic targets. The ability of microRNAs to modulate multiple signalling pathways simultaneously makes them particularly valuable tools for complex diseases such as heart failure," explained David de Gonzalo, head of the Clinical and Molecular Phenotyping (CMP) research group at IRBLleida. De Gonzalo, together with researcher María C. García-Hidalgo, are the two researchers from Lleida involved in the study.

The research was carried out as part of the European HOMAGE project and analysed blood samples from 799 elderly people to decipher the molecular pathways leading to heart failure and identify therapeutic targets suitable for pharmacological intervention. To do so, the research team combined advanced molecular analysis techniques with machine learning algorithms.

The study has identified three key microRNAs-miR-21-5p, miR-24-3p and miR-221-3p-as regulators of key pathobiological pathways in the progression of heart failure. By analysing the targets of these microRNAs in six independent datasets of human cardiac tissue, the researchers have mapped five essential molecular mechanisms: calcium homeostasis, cell proliferation and angiogenesis, stress response and cardiac remodelling, metabolic dysfunction, and neurohormonal activation.

microRNAs are small RNA molecules that regulate gene expression and can be easily detected in the blood. Their ability to simultaneously modulate multiple pathways makes them prime tools for understanding the pathophysiology of multifactorial diseases, and promising candidates for the development of next-generation therapies. Furthermore, the bioinformatic analysis carried out by the researchers identified the GABBR2 protein as a potential alternative therapeutic target. The study also highlights five drugs already approved by the US Food and Drug Administration (FDA) that could be the subject of future studies to assess their potential in the prevention or treatment of heart failure.

Article: de Gonzalo-Calvo D, García-Hidalgo MC, Chatterjee S, Thum S, Ferreira JP, Rossignol P, Girerd N, Verdonschot JA, Heymans S, Staessen JA, Cleland JG, Zannad F, Thum T, Bär C. Mechanistic insights into heart failure progression and therapeutic target discovery through plasma microRNA profiling: Findings from HOMAGE. Eur J Intern Med. 2026 May;147:106724. doi: 10.1016/j.ejim.2026.106724. Epub 2026 Jan 26. PMID: 41592979.