Abstract Number: PB0066
Meeting: ISTH 2020 Congress
Background: AMI has a high incidence in general population and high morbidity and mortality. Although the infarct process is multifactorial, atherosclerosis and inflammation play a relevant role. In this context, neutrophils and their extracellular traps (NETs) are crucial. Our group has described that miR-146a rs2431697 genotype influences NET formation.
Aims: We aimed to determine if young AMI patients have enhanced NETosis and evaluated their relationship with miR-146a genotype.
Methods: 300 AMI patients (41±4 years, 90% men) and 50 healthy blood donors (40±4 years, 90 % men) < 45 year-old 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 both, cell-free DNA (cfDNA) using SYTOX green and citrullinated histone-3 (citH3)/DNA by ELISA. Rs2431697 was genotyped using TaqMan probes. Finally, plasma DNaseI activity was determined in healthy donors (n=16) and in patients with normal (n=10) or high (more than 1.5-fold) levels of both cfDNA and citH3/DNA (n=47) respect to controls by ELISA.
Results: CfDNA and citH3/DNA levels in AMI patients were higher than in controls (p< 0.0001, and p< 0.0005, respectively) (Fig. 1A-B). These levels were increased in patients carrying the T allele of rs2431687 in comparison with CC patients (p< 0.05) (Fig. 1C). DNaseI activity was measured in patients with the highest cfDNA levels and citH3/DNA. Interestingly, DNaseI activity was significantly elevated in patients compared to controls. Additionally, 4 out of 47 AMI patients display low DNaseI activity compared to controls (1 with 50%, 2 with 25%, 1 with 5%).
Conclusions: These data show that plasma NET levels are significantly elevated in young AMI patients. On the other hand, miR-146a rs2431697 T allele may influences NET formation in these patients. Further investigation is required to determine the role of low DNaseI activity in AMI.
Funding: PI17/00051, PFIS18/0045, CM19/00037(ISCIII-FEDER), 19873/GERM/15, SETH.
To cite this abstract in AMA style:de los Reyes-García Pastor AM, Águila Martínez S, Arroyo Rodríguez AB, Orenes E, García Barberá N, Fernández Pérez MP, Reguilón Gallego L, Hernández Antolín R, Véliz A, López García C, Marín F, Vicente García V, Martínez Gómez C, González-Conejero Hilla R. MiR-146a Mediates Neutrophil Extracellular Traps Formation in Acute Myocardial Infarction (AMI) in Young Patients [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/mir-146a-mediates-neutrophil-extracellular-traps-formation-in-acute-myocardial-infarction-ami-in-young-patients/. Accessed August 15, 2022.
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