MicroRNA signatures of perioperative myocardial injury after elective noncardiac surgery: a prospective observational mechanistic cohort study

Abstract

Background: Elevated plasma or serum troponin, indicating perioperative myocardial injury (PMI), is common after noncardiac surgery. However, underlying mechanisms remain unclear. Acute coronary syndrome (ACS) is associated with the early appearance of circulating microRNAs, which regulate post-translational gene expression. We hypothesised that if PMI and ACS share pathophysiological mechanisms, common microRNA signatures should be evident. Methods: We performed a nested case control study of samples obtained before and after noncardiac surgery from patients enrolled in two prospective observational studies of PMI (postoperative troponin I/T>99th centile). In cohort one, serum microRNAs were compared between patients with or without PMI, matched for age, gender, and comorbidity. Real-time polymerase chain reaction quantified (qRTePCR) relative microRNA expression (cycle quantification [Cq] threshold <37) before and after surgery for microRNA signatures associated with ACS, blinded to PMI. In cohort two, we analysed (EdgeR) microRNA from plasma extracellular vesicles using next-generation sequencing (Illumina HiSeq 500). microRNA-messenger RNA-function pathway analysis was performed (DIANA miRPath v3.0/TopGO). Results: MicroRNAs were detectable in all 59 patients (median age 67 yr [61e75]; 42% male), who had similar clinical characteristics independent of developing PMI. In cohort one, serum microRNA expression increased after surgery (mean fold-change) hsa-miR-1-3p: 3.99 (95% confidence interval [CI: 1.95e8.19]; hsa-miR-133-3p: 5.67 [95% CI: 2.94e10.91]; P<0.001). These changes were not associated with PMI. Bioinformatic analysis of differentially expressed microRNAs from cohorts one (n¼48) and two (n¼11) identified pathways associated with adrenergic stress and calcium dysregulation, rather than ischaemia. Conclusions: Circulating microRNAs associated with cardiac ischaemia were universally elevated in patients after surgery, independent of development of myocardial injury.

Identification of Hub Genes and MicroRNAs Associated With Idiopathic Pulmonary Arterial Hypertension by Integrated Bioinformatics Analyses

“…The network suggested that hsa-mir-1-3p might regulate gene expression in IPAH. Previous studies have shown elevated hsa-mir-1-3p in perioperative myocardial injury patients ( May et al, 2020 ). Further research is needed to verify the mechanism linking hsa-mir-1-3p to IPAH.…”

In Vivo Stimulation of α- and β-Adrenoceptors in Mice Differentially Alters Small RNA Content of Circulating Extracellular Vesicles

“…For the control PBS-treated mouse group, the number of miRs classed by tags per million (TPM) interval were 438 miRs where TPM interval 0–3.57; the 139 miRs where TPM interval 3.57–15; the 117 miRs where TPM interval 15–60 and the 192 microRNAs where TPM > 60. In a recent study, human blood EVs and NGS study with the same analysis platform of ours, revealed 345 unique microRNA where TPM ≥ 1 and 164 unique microRNAs where TPM ≥ 10 [ 36 ].…”

The emergence of a postoperative myocardial injury epidemic: true or false?

“…40 Recent investigations using blood samples from the VISION 32 and METS 25 cohorts suggest myocardial injury has an inflammatory etiology. 41,42 Based on these facts, it is unlikely that all patients classified as having MINS had myocardial ischemia, and in my opinion, as an endpoint or a diagnosis, MINS is fundamentally flawed.…”

“…40 Des recherches récentes utilisant des échantillons de sang des cohortes des études VISION 32 et METS 25 suggèrent que la lésion myocardique aurait une étiologie inflammatoire. 41,42 Base´sur ces faits, il est peu probable que tous les patients classifie´s comme ayant une MINS souffraient d'une ische´mie myocardique, et a`mon avis, que ce soit comme crite`re d'e´valuation ou comme diagnostic, la MINS est fondamentalement errone´e.…”