Inflammasome activation dynamics within the first 24 hours in patients treated with PCI for myocardial infarction is influenced by the age of patients, preliminary report

Abstract

Abstract Funding Acknowledgements Type of funding sources: Public Institution(s). Main funding source(s): Presented study was financially supported by the Mini-student Grant for medical students of Medical University of Warsaw, No 24/M/MG/N/21 and Grant for Young Researchers of The Medical University of Warsaw, No 2W6/1/M/MBS/N/21. Background Until today, majority of data on the possible role of inflammasome activation in acute coronary syndrome (ACS) patients comes from preclinical studies. Purpose We aimed to determine the dynamics of the expression profile of selected inflammasome genes and inflammasome related factors by quantitative real-time polymerase chain reaction (qRT-PCR) in peripheral blood mononuclear cells (PBMCs) of patients in the acute phase of ACS. Methods In the study group the blood samples for RT-PCR were collected 3 times: at the beginning of the percutaneous coronary intervention (PCI) for ACS, 3h, and 24h after PCI. The study group samples were compared with blood collected from 10 patients with no significant coronary lesions identified during coronary angiography. The relative expression of evaluated genes was analyzed in relation to the β-actin gene in relation to the expression in 0-hour sample using the ΔΔCT method. Based on the literature, we defined a significant change in gene expression at a fold change of 1.5. Results For this preliminary study the population of 19 patients aged 64±13and 84% presented with ST-elevation myocardial infarction (STEMI). Expression of evaluated genes at 3h and 24h relative to 0h sample is presented in picture 1. Gene expression did not differ significantly between the study and control group except for NLR Family Pyrin Domain Containing 6 (NLRP6) (at 3h post-PCI: ΔΔCT=2.5425 vs 0.0005; p=0.002, 24h post-PCI: ΔΔCT=2.1794 vs 0.0005; p=0.009). However, we observed significant upregulation in samples taken at 3h post-PCI relative to 0h level for AIM2 [fold change relative to 0h 1.52 (0.63; 4.67)], IL-1β [2.81 (1.59; 5.93)], IL-18 [2.07 (0.59; 10.14)] and at 24 h for AIM2 [1.90 (0.78; 2.52)], IL-1β [5.16 (2.23; 13.32)] and IL-18 [2.20 (0.59; 5.96)] in the younger subgroup of patients (≤the median age of the study population which was equal 66 years old). We performed a comparison of younger (≤66) vs. older (>66) patients at 3h and 24h post-PCI and observed significantly higher relative gene expression in the younger subgroup compared to the older subgroup of patients at 3h in case of IL-1β (p=0.03), and at 24h in case of NLR Family Pyrin Domain Containing 1(NLRP1)(p=0.016), AIM2 (p=0.04), NLR Family Pyrin Domain Containing 12(NRLP12)(p=0.06), IL-1 (p=0.04), and IL-18 (p=0.03) – the exact fold change values are presented in Table 1. Conclusion NLRP6 is significantly upregulated in ACS patients compared to control subjects in the first 24h post-PCI. We also observed significant dynamics in NLRP3 inflammasome related factors, including IL-1β, IL-18, in the first 24h post-PCI for MI. Also, the activation of the inflammasome genes (NLRP1, NLRP12) and inflammasome effectors may present different dynamics dependent on the age of the patients, and it might be helpful in careful selection of the timepoint for the future administration of inflammasome dedicated inhibitors.Relative genes expressionFold change in gene expression