BibTex format
@article{Tikhomirov:2026:10.1161/CIRCRESAHA.125.326799,
author = {Tikhomirov, R and Boichenko, V and Reilly-O'Donnell, B and Lucarelli, C and Srivastava, PK and Anwar, M and Yiu, CHK and Dielesen, J and Noakes, VM and Piella, SN and Kazharova, D and Labbé, M and Kwan, Z and Zaccagnini, G and Mansfield, C and Tessari, M and Menicanti, L and Greco, S and Sweeney, M and Okafor, J and Leszek, P and Faggian, G and Luciani, GB and Emanueli, C and Martelli, F and Gorelik, J},
doi = {10.1161/CIRCRESAHA.125.326799},
journal = {Circ Res},
title = {Interleukin 11-Induced MicroRNAs as Functional Mediators and Circulating Biomarkers of Cardiac Fibrosis.},
url = {http://dx.doi.org/10.1161/CIRCRESAHA.125.326799},
volume = {138},
year = {2026}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - BACKGROUND: Cardiac fibrosis can be triggered by several pathologies, including ischemic heart disease and aortic stenosis. Cardiac fibrosis is brought about by uncontrolled ECM (extracellular matrix) deposition by myofibroblasts. IL (interleukin)-11 (Il11) has been demonstrated as a trigger of multiorgan fibrosis. However, the molecular mechanisms underpinning IL-11-induced fibrosis require further characterization. Recent studies indicate that microRNA dysregulation contributes to the pathogenesis of cardiac fibrosis and can be targeted therapeutically. This study explored the hypothesis that microRNAs act as downstream effectors of IL-11-induced cardiac fibrosis. Moreover, we investigated the translational potential of IL-11-regulated microRNAs as circulating biomarkers of cardiac fibrosis in patients with aortic stenosis. METHODS: A bioinformatic microRNA target prediction analysis was used to identify candidate microRNAs regulated by IL-11. Experimental validation was performed in cardiac fibroblasts from postinfarction failing and healthy rat hearts, after IL-11 stimulation. Functional studies assessed the effects of microRNA modulation on fibrotic gene expression in cardiac fibroblasts using microRNA inhibitor-based and mimic-based transfection. Bioinformatic analysis and luciferase assay identified candidate microRNA targets downstream of IL-11. Findings were further evaluated in transverse aortic constriction and cardiomyocyte-specific Il11-overexpression (Tg-Il11 [transgenic mouse model with cardiomyocyte-specific Il11 overexpression]) mouse models and in left ventricular tissue, peripheral plasma, and plasma extracellular vesicles from patients with aortic stenosis. RESULTS: MicroRNA-27b-5p and microRNA-497-5p were identified as novel downstream effectors of IL-11 signaling. IL-11 increased the expression of both microRNAs in cardiac fibroblasts; transfection with either microRNA inhibitor reduced, whereas microRNA mimics increased, profibrotic mRNA level
AU - Tikhomirov,R
AU - Boichenko,V
AU - Reilly-O'Donnell,B
AU - Lucarelli,C
AU - Srivastava,PK
AU - Anwar,M
AU - Yiu,CHK
AU - Dielesen,J
AU - Noakes,VM
AU - Piella,SN
AU - Kazharova,D
AU - Labbé,M
AU - Kwan,Z
AU - Zaccagnini,G
AU - Mansfield,C
AU - Tessari,M
AU - Menicanti,L
AU - Greco,S
AU - Sweeney,M
AU - Okafor,J
AU - Leszek,P
AU - Faggian,G
AU - Luciani,GB
AU - Emanueli,C
AU - Martelli,F
AU - Gorelik,J
DO - 10.1161/CIRCRESAHA.125.326799
PY - 2026///
TI - Interleukin 11-Induced MicroRNAs as Functional Mediators and Circulating Biomarkers of Cardiac Fibrosis.
T2 - Circ Res
UR - http://dx.doi.org/10.1161/CIRCRESAHA.125.326799
UR - https://www.ncbi.nlm.nih.gov/pubmed/41841256
VL - 138
ER -