Circulating miRNA Fingerprint and Endothelial Function in Myocardial Infarction: Comparison at Acute Event and One-Year Follow-Up

Cells. 2022 Jun 2;11(11):1823. doi: 10.3390/cells11111823.

Abstract

MicroRNAs (miRNA) are major regulators of intercellular communication and key players in the pathophysiology of cardiovascular disease. This study aimed to determine the miRNA fingerprint in a cohort of 53 patients with acute myocardial infarction (AMI) with non-ST-segment elevation (NSTEMI) relative to miRNA expression in healthy controls (n = 51). miRNA expression was initially profiled by miRNA array in the serum of patients undergoing cardiac catheterization during NSTEMI (n = 8) and 1 year past the event (follow-up, n = 8) and validated in the entire cohort. In total, 58 miRNAs were differentially expressed during AMI (p < 0.05), while 36 were modified at follow-up (Fisher’s exact test: p = 0.0138). Enrichment analyses revealed differential regulation of biological processes by miRNA at each specific time point (AMI vs. follow-up). During AMI, the miRNA profile was associated mainly with processes involved in vascular development. However, 1 year after AMI, changes in miRNA expression were partially related to the regulation of cardiac tissue morphogenesis. Linear correlation analysis of miRNA with serum levels of cytokines and chemokines revealed that let-7g-5p, let-7e-5p, and miR-26a-5p expression was inversely associated with serum levels of pro-inflammatory cytokines TNF-α, and the chemokines MCP-3 and MDC. Transient transfection of human endothelial cells (HUVEC) with let-7e-5p inhibitor or mimic demonstrated a key role for this miRNA in endothelial function regulation in terms of cell adhesion and angiogenesis capacity. HUVEC transfected with let-7e-5p mimic showed a 20% increase in adhesion capacity, whereas transfection with let-7e-5p inhibitor increased the number of tube-like structures. This study pinpoints circulating miRNA expression fingerprint in NSTEMI patients, specific to the acute event and changes at 1-year follow-up. Additionally, given its involvement in modulating endothelial cell function and vascularization, altered let-7e-5p expression may constitute a therapeutic biomarker and target for ischemic heart disease.

Keywords: angiogenesis; endothelial cell; let-7e; microRNA profile; myocardial infarction; serum biomarker.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circulating MicroRNA* / genetics
  • Cytokines
  • Endothelial Cells / metabolism
  • Follow-Up Studies
  • Humans
  • MicroRNAs* / metabolism
  • Myocardial Infarction* / genetics
  • Non-ST Elevated Myocardial Infarction*

Substances

  • Circulating MicroRNA
  • Cytokines
  • MicroRNAs

Grants and funding

This research was funded by Spanish Ministerio de Ciencia, e Innovación, Instituto de Salud Carlos III-FEDER-ERDF (grants PI13/00617, PI13/00091, PI16/00229, PI16/00742, PI19/01714, PI19/00264, RD12/0042/0052, and RD12/0042/0006), Generalitat Valenciana (AICO 2020/030), and COST Action (CA17129: CardioRNA). A.M. is a “Formación de Profesorado Universitario” fellow (grant number FPU13/02235 Spanish Ministerio de Educación, Cultura y Deporte). D.P.-C. is a “Juan de la Cierva-Incorporación” fellow (grant number IJC2019-040237-I) from the Spanish Ministerio de Ciencia e Innovación. A.B.P. is a predoctoral researcher (FI18/00323) from Instituto de Salud Carlos III.