OC 18.3 - MiR-146a seeds a pro-inflammatory state in acute myocardial infarction of young patients promoting recurrence

Sunday, July 10, 2022

11:15 AM – 11:30 AM

Location: ExCel Center, ICC Capital Suite Room 2-4

Presentation Format: In-Person

Presenting Author(s)

Ascensión M. de los Reyes-García, MSc

PhD student
Instituto Murciano de Investigación Biomédica, Universidad de Murcia, Hospital Universitario Morales Meseguer
Murcia, Murcia, Spain

Co-Author(s)

JR

José Miguel Rivera Caravaca

Dr.
Hospital Virgen de la Arrixaca
Murcia, Murcia, Spain
SA

Sonia Aguila Martinez

PI
Centro Regional de Hemodonación
Murcia, Murcia, Spain
NG

Nuria García-Barberá

Mss
CENTRO REGIONAL DE HEMODONACIÓN. HOSPITAL MORALES MESEGUER. UNIVERSIDAD DE MURCIA. IMIB-ARRIXACA
Murcia, Murcia, Spain
LZ

Laura Zapata-Martínez

MSC
CENTRO REGIONAL DE HEMODONACIÓN. HOSPITAL MORALES MESEGUER. UNIVERSIDAD DE MURCIA. IMIB-ARRIXACA
Murcia, Murcia, Spain
ML

María Luisa Lozano

Leader of Hematology Service in Murcia
Servicio de Hematología y Oncología Médica, Hospital Universitario Morales Meseguer, Centro Regional de Hemodonación, Universidad de Murcia, IMIB-Pascual Parrilla, CIBERER, Murcia, Spain
Murcia, Murcia, Spain
FM

Francisco Marín

MD.
Hospital Virgen de la Arrixaca
Murcia, Murcia, Spain
CM

Constantino Martínez

Dr.
CENTRO REGIONAL DE HEMODONACIÓN. HOSPITAL MORALES MESEGUER. UNIVERSIDAD DE MURCIA. IMIB-ARRIXACA
Murcia, Murcia, Spain
RG

Rocío Gonzalez-Conejero Hilla

Professor
CENTRO REGIONAL DE HEMODONACIÓN. HOSPITAL MORALES MESEGUER. UNIVERSIDAD DE MURCIA. IMIB-ARRIXACA
Murcia, Murcia, Spain

Background: Inflammation and atherosclerosis have an important function in acute coronary syndrome (ACS). Neutrophils are responsible for one of the most important elements involved in thrombosis/inflammation crosstalk, neutrophil extracellular traps (NETs). miR-146a-5p has important anti-inflammatory functions. Our group previously described that its levels are regulated by rs2431697 influencing NET formation. Here, we evaluated the potential association between NET markers and outcomes of ACS in young adults ( < 45 years).

Aims: In these subjects, differences in etiology and risk factors may lead the prognosis and treatments. Therefore, an early detection of subclinical disease might prevent coronary events or recurrences.

Methods: 300 ACS patients (44±4 years) and 300 healthy blood donors (44±4 years) were recruited. The informed consent was obtained for each subject and the study was approved by local ethics committee . NETs in plasma were evaluated by quantifying cell-free DNA (cfDNA) using SYTOX green, and citrullinated histone-3 (citH3)/DNA complexes by ELISA. Rs2431697 was genotyped using TaqMan probes. Patients were followed-up up from January 2015 until March 2020 and all adverse events were recorded.

Results: We found a positive correlation between citH3-DNA complexes and cfDNA levels with Killip-Kimball score (p=0.002 and p< 0.001), suggesting that patients with more severe ACS had higher levels of NETosis. We also found higher Killip-Kimball score in those patients with cfDNA levels above Q4 (p=0.003). Patients with citH3-DNA levels above Q4 had more stroke recurrence (p=0.026). Finally, when cfDNA and citH3-DNA levels were combined with the T allele of rs2431697 as a risk factor, we found a higher risk of ischemic event recurrence (p=0.024).

Conclusion(s): The present research shows an association between NETs’ markers and rs2431697 T allele increasing the risk of recurrence of cardiovascular events in young patients with ACS. These findings support the clinical relevance of circulating NETs as novel markers in ACS and as a potential therapeutic target.