Pericardial fluid (PF) has been suggested as a reservoir of molecular targets that can be modulated for efficient repair after myocardial infarction (MI). Here, we set out to address the content of this biofluid after MI, namely in terms of microRNAs (miRs) that are important modulators of the cardiac pathological response. PF was collected during coronary artery bypass grafting (CABG) from two MI cohorts, patients with non-ST-segment elevation MI (NSTEMI) and patients with ST-segment elevation MI (STEMI), and a control group composed of patients with stable angina and without previous history of MI. The PF miR content was analyzed by small RNA sequencing, and its biological effect was assessed on human cardiac fibroblasts. PF accumulates fibrotic and inflammatory molecules in STEMI patients, namely causing the soluble suppression of tumorigenicity 2 (ST-2), which inversely correlates with the left ventricle ejection fraction. Although the PF of the three patient groups induce similar levels of fibroblast-to-myofibroblast activation in vitro, RNA sequencing revealed that PF from STEMI patients is particularly enriched not only in pro-fibrotic miRs but also anti-fibrotic miRs. Among those, miR-22-3p was herein found to inhibit TGF-β-induced human cardiac fibroblast activation in vitro. PF constitutes an attractive source for screening diagnostic/prognostic miRs and for unveiling novel therapeutic targets in cardiac fibrosis.

Cardiovascular R and D Center Faculty of Medicine University of Porto 4150 180 Porto Portugal

Center for Translational Health and Medical Biotechnology Research ESS Polytechnic of Porto 4200 072 Porto Portugal

Center for Translational Medicine St Anne's Hospital 60200 Brno Czech Republic

Chemical and Biomolecular Sciences School of Health Polytechnic of Porto 4200 465 Porto Portugal

Department of Biomedical Sciences Faculty of Medicine Masaryk University 62500 Brno Czech Republic

i3S Institute for Research and Innovation in Health University of Porto 4200 135 Porto Portugal

ICBAS Instituto de Ciências Biomédicas Abel Salazar University of Porto 4050 313 Porto Portugal

INEB Instituto Nacional de Engenharia Biomédica University of Porto 4200 135 Porto Portugal

INL International Iberian Nanotechnology Laboratory 4715 330 Braga Portugal

Instituto de Medicina Molecular João Lobo Antunes Faculdade de Medicina Universidade de Lisboa 1649 028 Lisbon Portugal

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