Exosomal microRNA‑4516, microRNA‑203 and SFRP1 are potential biomarkers of acute myocardial infarction

Abstract

Acute myocardial infarction (AMI) is a serious disease which threatens public health. Exosomes (exos) contain certain genetic information and are important communication vehicles between cells. In the present study, different exosomal microRNAs (miRs), which exhibit a notable association between expression levels in plasma and AMI were assessed to support the development of new diagnostic and clinical assessment markers of patients with AMI. In total, 93 individuals, including 31 healthy controls and 62 patients with AMI, were recruited for the present study. Data on age, blood pressure, glucose levels, lipid levels and coronary angiography images were collected from the enrolled individuals, and plasma samples were collected. Plasma exos were extracted and verified using ultracentrifugation, transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA) and western blotting (WB). Exo-miR-4516 and exo-miR-203 in plasma exos were identified by exosomal miRNA sequencing analysis, reverse transcription-quantitative PCR was performed to detect the levels of exo-miR-4516 and exo-miR-203 in plasma exos, and ELISA was performed to detect the levels of secretory frizzled-related protein 1 (SFRP1) in samples. The correlation analysis between exo-miR-4516, exo-miR-203 and SFRP1 in plasma exos and AMI was presented as receiver operating characteristic curves (ROCs) of the SYNTAX score, cardiac troponin I (cTnI), low-density lipoprotein (LDL) and each indicator separately. Kyoto Encyclopedia of Genes and Genomes enrichment analysis was performed to predict relevant enrichment pathways. Exos were successfully isolated from plasma by ultracentrifugation, which was confirmed by TEM, NTA and WB. Exo-miR-4516, exo-miR-203 and SFRP1 levels in plasma were significantly higher in the AMI group compared with the healthy control group. ROCs demonstrated that exo-miR-4516, exo-miR-203 and SFRP1 levels had a high diagnostic efficiency in predicting AMI. Exo-miR-4516 was positively correlated with SYNTAX score, and plasma SFRP1 was positively correlated with plasma cTnI and LDL. In conclusion, the data demonstrated that exo-miR-4516, exo-miR-203 and SFRP1 levels could be used in combination to diagnose and assess the severity of AMI. The present study was retrospectively registered (TRN, NCT02123004).

Unraveling the Signaling Dynamics of Small Extracellular Vesicles in Cardiac Diseases

“…Some analyses of circulating exosomes in the serum of MI patients have revealed a large number of miRNAs that are deregulated. For example, miR-203, miR-4516, or miR-183, which regulate the activity of several protein kinases in CMs, are upregulated, confirming their identification as MI biomarkers [67,70]. Another transcriptomic study identifies the deregulation of miRNA levels in exosomes on a large scale, identifying around 500 upregulated and downregulated miRNAs in MI exosomes, highlighting miR-6718 and miR-4329 [68].…”

“…Multiple lines of evidence have also been reported, indicating that such exosome-mediated cellular communication is altered and impaired in pathological conditions, particularly in oncogenesis [4,11]. More recently, impaired exosome signaling has also been reported in distinct cardiovascular pathological contexts, including ischemic [67][68][69], electrical [280][281][282][283][284][285][286] and structural [215,223] cardiopathies. It is important to highlight in this context that increasing evidence is reported about the functional role of exosomes in distinct ischemic diseases, such as MI and coronary artery diseases, as well as in structural heart diseases such as DCM and HCM, as reviewed in this study.…”

“…Currently, the main diagnostic biomarker for MI is cardiac troponin (T/I) [64], even though other more sensitive biomarkers have emerged, for example, non-coding RNAs, which allow for an earlier diagnosis [65,66]. Within non-coding RNAs, an increasing number of transcriptomic studies identified miRNAs in exosomes after MI [67][68][69]. Some analyses of circulating exosomes in the serum of MI patients have revealed a large number of miRNAs that are deregulated.…”

Ispinesib Mesylate-induced oxidative stress via miR-30e-5p/BCL2L11 axis in acute myocardial infarction: a comprehensive bioinformatics and experimental validation investigation

“…Furthermore, we executed Real-Time Quantitative Polymerase Chain Reaction (RT-qPCR) and Lentivirus infection experiments via cellular experimentation to validate these pivotal genes, whilst employing Mendelian Randomization to probe into the potential causal association between BCL2L11 and AMI [29]. Ultimately, we devised a network model encompassing the miR-30e-5p/BCL2L11 axis, and identi ed two prospective novel medications for the management and treatment of AMI through drug susceptibility analysis: Ispinesib Mesylate and Bleomycin (50 uM) [30].…”