Pericardial Fluid Accumulates microRNAs That Regulate Heart Fibrosis after Myocardial Infarction

Author:

Silva Elsa D.123,Pereira-Sousa Daniel1245ORCID,Ribeiro-Costa Francisco13,Cerqueira Rui6ORCID,Enguita Francisco J.7ORCID,Gomes Rita N.123ORCID,Dias-Ferreira João13ORCID,Pereira Cassilda1389ORCID,Castanheira Ana1310,Pinto-do-Ó Perpétua123,Leite-Moreira Adelino F.6ORCID,Nascimento Diana S.123ORCID

Affiliation:

1. i3S—Institute for Research and Innovation in Health, University of Porto, 4200-135 Porto, Portugal

2. ICBAS—Instituto de Ciências Biomédicas Abel Salazar, University of Porto, 4050-313 Porto, Portugal

3. INEB—Instituto Nacional de Engenharia Biomédica, University of Porto, 4200-135 Porto, Portugal

4. Center for Translational Medicine (CTM), International Clinical Research Centre (ICRC), St. Anne’s Hospital, 60200 Brno, Czech Republic

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

6. Cardiovascular R&D Center, Faculty of Medicine, University of Porto, 4150-180 Porto, Portugal

7. Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, 1649-028 Lisbon, Portugal

8. Center for Translational Health and Medical Biotechnology Research (TBIO)/Health Research Network (RISE-Health), ESS, Polytechnic of Porto, 4200-072 Porto, Portugal

9. Chemical and Biomolecular Sciences, School of Health (ESS), Polytechnic of Porto, 4200-465 Porto, Portugal

10. INL—International Iberian Nanotechnology Laboratory, 4715-330 Braga, Portugal

Abstract

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.

Funder

INFARMED—Autoridade Nacional do Medicamento e Produtos de Sau’de

European Regional Development Fund

FCT/Ministério da Ciência, Tecnologia e Inovação

individual funding

Publisher

MDPI AG

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