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.

• Klíčová slova
• cardiac fibroblasts, fibrosis, miR-22-3p, miRNAs, myocardial infarction, pericardial fluid,
• MeSH
• fibroblasty metabolismus   MeSH
• fibróza * MeSH
• infarkt myokardu s elevacemi ST úseků metabolismus   patologie   genetika   MeSH
• infarkt myokardu * metabolismus   genetika   patologie   MeSH
• interleukin-1 receptor-like 1 protein metabolismus   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * genetika   metabolismus   MeSH
• myokard metabolismus   patologie   MeSH
• perikardiální tekutina * metabolismus   MeSH
• senioři MeSH
• transformující růstový faktor beta metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• IL1RL1 protein, human MeSH Prohlížeč
• interleukin-1 receptor-like 1 protein MeSH
• mikro RNA * MeSH
• MIRN22 microRNA, human MeSH Prohlížeč
• transformující růstový faktor beta MeSH

Current knowledge on the renin-angiotensin system (RAS) indicates its central role in the pathogenesis of cardiovascular remodelling via both hemodynamic alterations and direct growth and the proliferation effects of angiotensin II or aldosterone resulting in the hypertrophy of cardiomyocytes, the proliferation of fibroblasts, and inflammatory immune cell activation. The noncoding regulatory microRNAs has recently emerged as a completely novel approach to the study of the RAS. A growing number of microRNAs serve as mediators and/or regulators of RAS-induced cardiac remodelling by directly targeting RAS enzymes, receptors, signalling molecules, or inhibitors of signalling pathways. Specifically, microRNAs that directly modulate pro-hypertrophic, pro-fibrotic and pro-inflammatory signalling initiated by angiotensin II receptor type 1 (AT1R) stimulation are of particular relevance in mediating the cardiovascular effects of the RAS. The aim of this review is to summarize the current knowledge in the field that is still in the early stage of preclinical investigation with occasionally conflicting reports. Understanding the big picture of microRNAs not only aids in the improved understanding of cardiac response to injury but also leads to better therapeutic strategies utilizing microRNAs as biomarkers, therapeutic agents and pharmacological targets.

• Klíčová slova
• RAS, cardiac fibrosis, cardiac hypertrophy, cardiac remodelling, miRNA,
• MeSH
• fibróza MeSH
• kardiomegalie genetika   metabolismus   patologie   MeSH
• lidé MeSH
• mikro RNA genetika   metabolismus   MeSH
• myokard metabolismus   patologie   MeSH
• nemoci srdce genetika   metabolismus   patologie   MeSH
• renin-angiotensin systém * MeSH
• signální transdukce * MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• mikro RNA MeSH