Work

BM-164 (an H₂S-donor) modulates microRNA expression associated with reperfusion-induced ventricular fibrillation in rat hearts

Year: 2026

Type: article

Abstract: • Ventricular arrhythmias are a leading cause of sudden cardiac death in myocardial infarction and heart failure. • BM-164, a hydrogen sulfide donor, modulates cardiac microRNA profiles after ischemia/reperfusion (I/R) injury. • Ischemia-associated miRNAs were identified by Nanostring and validated with qPCR, revealing differences between groups with and without ventricular fibrillation (VF). • BM-164 and ascorbic acid altered miRNAs linked to apoptosis and autophagy (rno-miR-30d, -99a, -130a, -133a, -181a, -191a). • In silico analysis indicated that the studied miRNAs are linked to cardioprotective pathways. • The results are associative; further in vitro and in vivo studies are required to establish causal relationships. Ventricular arrhythmias are a leading cause of sudden cardiac death in myocardial infarction and heart failure. Reperfusion following ischemia can trigger severe arrhythmias, including ventricular fibrillation (VF), and microRNAs (miRNAs) which are increasingly recognized as critical regulators of these processes. This study aimed to identify miRNAs associated with ischemia/reperfusion (I/R)-induced ventricular fibrillation by comparing expression profiles between fibrillated (VF) and non-fibrillated (No VF) rat hearts. Nanostring-based screening (n = 12; 4 in each group: No I/R control, I/R no VF, and I/R VF) identified several ischemia-associated miRNAs, including rno-miR-30d, rno-miR-99a, rno-miR-130a, rno-miR-133a, rno-miR-181a, and rno-miR-191a. These candidates were subsequently validated in a larger cohort using TaqMan qRT-PCR (qPCR), including BM-164- and ascorbic acid (AA)-pretreated I/R groups administered 10 minutes before I/R (n = 6 per group). The selection of these miRNAs was guided by prior literature demonstrating their established roles in ischemia-related pathways and cardioprotection, providing a biologically grounded rationale for their inclusion. qPCR analysis, compared with Nanostring data on a Rat miRNA panel v1.5 (425 miRNAs), revealed significant alterations in a subset of these miRNAs in I/R hearts, particularly in VF-affected samples. BM-164, an H ₂ S-donor, and to a lesser extent AA, were associated with partial restoration or upregulation of these miRNAs. These findings suggest that the examined miRNAs, particularly miR-99a, miR-191a, miR-30d, and miR-181a, are likely involved in the development of reperfusion-induced ventricular arrhythmias. BM-164 pretreatment was associated with changes of these miRNAs, which have been previously implicated in autophagy and apoptosis pathways; further studies are warranted to determine whether these alterations directly mediate cardioprotection or anti-arrhythmic effects. Given the limited sample size, these findings should be considered preliminary. Larger cohorts and additional in vivo studies are required to clarify whether these miRNA alterations causally contribute to arrhythmogenesis or represent protective responses.

Source: European Journal of Pharmaceutical Sciences

DOI: 10.1016/j.ejps.2026.107433

Authors: E. Szabó, J. Király, A.B. Mondal, I. Bereczki, Z. Szabó, Á. Tósaki

Institution: University of Debrecen

Language: English

Topic: Cardiac Ischemia and Reperfusion

Subfield: Pathology and Forensic Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,070