Predicted Value of MicroRNAs, Vascular Endothelial Growth Factor, and Intermediate Monocytes in the Left Adverse Ventricular Remodeling in Revascularized ST-Segment Elevation Myocardial Infarction Patients

Raquel Del Toro; Isabel Galeano-Otero; Elisa Bevilacqua; Francisco Guerrero-Márquez; Debora Falcon; Agustín Guisado-Rasco; Luis Díaz-de la Llera; Gonzalo Barón-Esquivias; Tarik Smani; Antonio Ordóñez-Fernández

doi:10.3389/fcvm.2022.777717

Predicted Value of MicroRNAs, Vascular Endothelial Growth Factor, and Intermediate Monocytes in the Left Adverse Ventricular Remodeling in Revascularized ST-Segment Elevation Myocardial Infarction Patients

Front Cardiovasc Med. 2022 Mar 24:9:777717. doi: 10.3389/fcvm.2022.777717. eCollection 2022.

Authors

Affiliations

¹ Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Seville, Spain.
² Grupo de Fisiopatología Cardiovascular, Instituto de Biomedicina de Sevilla-IBiS, Universidad de Sevilla/HUVR/Junta de Andalucía/CSIC, Seville, Spain.
³ Servicio de Cardiología, Hospital Universitario Virgen del Rocío, Seville, Spain.

Abstract

Background: Primary percutaneous coronary intervention (PPCI) in patients with ST-segment elevation myocardial infarction (STEMI) improves the survival of patients; nevertheless, some patients develop left ventricular adverse remodeling (LVAR) a few months after the intervention. The main objective of this study was to characterize the role of pro-inflammatory cell populations, related cytokines, and microRNAs (miRNAs) released after PPCI as reliable prognostic biomarkers for LVAR in patients with STEMI.

Methods: We evaluated the level of pro-inflammatory subsets, before and after revascularization, 1 and 6 months after PPCI, using flow cytometry. We also performed a miRNA microarray in isolated peripheral blood mononuclear cells (PBMCs) and examined the levels of 27 cytokines in patients' serum of patients by multiplex ELISA.

Results: We observed that the levels of classical and intermediate monocytes increased 6 h after PPCI in patients who developed LVAR later. Multivariate regression analysis and ROC curves indicated that intermediate monocytes, after PPCI, were the best monocyte subset that correlated with LVAR. Within the 27 evaluated cytokines evaluated, we found that the increase in the level of vascular endothelial growth factor (VEGF) correlated with LVAR. Furthermore, the microarray analysis of PBMCs determined that up to 1,209 miRNAs were differentially expressed 6 h after PPCI in LVAR patients, compared with those who did not develop LVAR. Using RT-qPCR we confirmed a significant increase in miR-16, miR-21-5p, and miR-29a-3p, suggested to modulate the expression of different cytokines, 6 h post-PPCI in LVAR patients. Interestingly, we determined that the combined analysis of the levels of the intermediate monocyte subpopulation, VEGF, and miRNAs gave a better association with LVAR appearance. Similarly, combined ROC analysis provided high accurate specificity and sensibility to identify STEMI patients who will develop LVAR.

Conclusion: Our data suggest that the combined analysis of intermediate monocytes, VEGF, and miRNAs predicts LVAR in STEMI patients.

Keywords: PPCI; STEMI; inflammatory cells; left ventricular adverse remodeling; monocytes.