MiR-146a Contributes to Thromboinflammation and Recurrence in Young Patients with Acute Myocardial Infarction.
Ascensión María de Los Reyes-GarcíaJose Miguel Rivera-CaravacaLaura Zapata-MartínezSonia ÁguilaAndrea Véliz-MartínezNuria García-BarberáPablo Gil-PerezPedro J Guijarro-CarrilloEsteban Orenes-PiñeroCecilia López-GarcíaMaría Luisa LozanoFrancisco MarínConstantino MartínezRocío González-ConejeroPublished in: Journal of personalized medicine (2022)
Studies on older patients have established notable conceptual changes in the etiopathogenesis of acute coronary syndrome (ACS), but little is known about this disease in young patients (<45 years). Of special interest is thromboinflammation, key at onset, evolution and therapy of cardiovascular pathology. Therefore, we explored whether ACS at an early age is a thromboinflammatory disease by analyzing NETs and rs2431697 of miR-146a (a miRNA considered as a brake of TLR/NF-kB pathway), elements previously related to higher rates of recurrence in atrial fibrillation and sepsis. We included 359 ACS patients (<45 years) and classified them for specific analysis into G1 (collected during the hospitalization of the first event), G2 and G3 (retrospectively collected from patients with or without ACS recurrence, respectively). cfDNA and citH3-DNA were quantified, and rs2431697 was genotyped. Analysis in the overall cohort showed a moderate but significant correlation between cfDNA and citH3-DNA and Killip-Kimball score. In addition, patients with citH3-DNA > Q4 more frequently had a history of previous stroke (6.1% vs. 1.6%). In turn, rs2431697 did not confer increased risk for the onset of ACS, but T carriers had significantly higher levels of NET markers. By groups, we found that cfDNA levels were similarly higher in all patients, but citH3-DNA was especially higher in G1, suggesting that in plasma, this marker may be attenuated over time. Finally, patients from G2 with the worst markers (cfDNA and citH3-DNA > Q2 and T allele) had a two-fold increased risk of a new ischemic event at 2-year follow-up. In conclusion, our data confirm that ACS is younger onset with thromboinflammatory disease. In addition, these data consolidate rs2431697 as a silent proinflammatory factor predisposing to NETosis, and to a higher rate of adverse events in different cardiovascular diseases.
Keyphrases
- acute coronary syndrome
- end stage renal disease
- atrial fibrillation
- newly diagnosed
- ejection fraction
- acute myocardial infarction
- peritoneal dialysis
- prognostic factors
- long non coding rna
- single molecule
- circulating tumor
- immune response
- heart failure
- intensive care unit
- stem cells
- oxidative stress
- patient reported outcomes
- left ventricular
- toll like receptor
- acute kidney injury
- electronic health record
- big data
- nucleic acid
- data analysis
- left atrial
- mesenchymal stem cells
- nuclear factor
- free survival
- catheter ablation
- subarachnoid hemorrhage