Šimonytė, Sandrita

The formation of extracellular traps (ETs) through ETosis has emerged as a key mechanism in immunothrombosis. However, the temporal dynamics and clinical significance of ETosis in coronary thrombi of ST-elevation myocardial infarction (STEMI) patients remain incompletely understood. We investigated whether ETosis burden increases with thrombus age and is associated with DNASE1 and TREX1 genetic variants as well as impaired myocardial reperfusion. Thrombus aspirates from 81 STEMI patients undergoing primary percutaneous coronary intervention were histologically classified as fresh (n = 41) or lytic (n = 40). ETosis was quantified by citrullinated histone H3 (CitH3) immunohistochemistry and digital image analysis, complemented by multiplex staining for myeloperoxidase (MPO), CD68, caspase 3, and CD61. Plasma ET-related markers and genotyping of DNASE1 (rs1053874) and TREX1 (rs11797) were also performed. CitH3-positive cells were present in all thrombi but were more abundant in lytic (older) thrombi compared with fresh thrombi (1348 vs. 591 cells/mm2, p < 0.001). Increased ETosis was associated with neutrophil and macrophage infiltration, apoptosis, prolonged ischemia time, elevated systemic inflammation (neutrophil–lymphocyte ratio and C-reactive protein), and impaired myocardial reperfusion (lower TIMI flow grades). Moreover, the DNASE1 GG genotype was associated with higher densities of MPO- and CD68-positive cells, whereas the TREX1 CC genotype was associated with increased densities of CitH3-, MPO-, and CD68-positive cells. This study demonstrates that ETosis increases with coronary thrombus maturation and is associated with local inflammation and impaired reperfusion in STEMI. Genetic variants in DNASE1 and TREX1 may modulate inflammatory cell accumulation within thrombi. These findings suggest ETosis as a potential therapeutic target, particularly in patients with delayed presentation.

Introduction/Aim: People who had been admitted to intensive care with SARS-CoV-2 acute infection after recovery during the next year had an increased risk of developing a higher rate of cardiovascular complications, including cases of myocardial infarctions. It has been demonstrated that COVID-19 increases the levels of intracellular reactive oxygen species in neutrophils to stimulate neutrophil extracellular traps (NETs) formation which contribute DNA burden and thrombosis, including ST-segment elevation myocardial infarction (STEMI). This study aim was to determine and evaluate biomarkers of NET in the blood plasma of patients with acute myocardial infarction after COVID-19 disease. Material and Methods: Patients’ blood plasma samples were used in this study. 53 patients with acute MI (AMI) and with a history of COVID-19 disease were enrolled in the experimental group. The control group comprised 52 patients who had previously tested negative for COVID-19 disease. Quantitative ELISA method and quantitative fluorescence spectroscopy method was used to measure the concentration of NET biomarkers. The difference was considered statistically significant at the value of p < 0.05. Results: Patients of experimental group had significantly higher plasma MPO concentration compared to the control group (p = 0,049). The possibility of having AMI after COVID-19 disease was found to be up to 2,5 times higher with MPO blood levels greater than or equal to 42,81 ng/ml (vs < 42,81 ng/ml) (OR = 2,713, p = 0,022). Conclusions: The concentration of MPO was significantly higher in COVID-19 recovered patients who later experienced an acute myocardial infarction compared to those with no history of COVID-19 disease. A concentration of the neutrophil extracellular traps’ component MPO greater than or equal to 42,81 ng/ml (vs < 42,81 ng/ml) significantly contributes to the development of acute myocardial infarction after COVID-19 disease.

2019 m. pabaigoje pradėjęs plisti SARS-CoV-2 virusas, kurį Pasaulio sveikatos organizacija greitai pripažino globalia sveikatos problema, iki šiol kelia didelių iššūkių visuomenės sveikatos priežiūros sektoriui. Nuo pandemijos pradžios buvo aiškiai nustatyti pagrindiniai šio viruso sukeliamos ūminės COVID-19 ligos simptomai, komplikacijos ir galimos baigtys. Tik vėliau pastebėta, kad daliai persirgusių asmenų pasireiškia ilgalaikis šio viruso poveikis sveikatai, šiems asmenims atsiranda požymių ir simptomų, kurie išlieka ilgiau nei 12 sav., nėra paaiškinami kitomis diagnozėmis ir perspėja apie galimą pokovidinį sindromą. Naujausi tyrimai rodo, kad šis sindromas padidina ūminio miokardo infarkto riziką ir yra rimtas širdies ir kraujagyslių ligų vystymosi veiksnys. COVID-19 tema vis dar aktuali dėl ribotų žinių apie mechanizmus, siejančius pokovidinį sindromą su ūminio miokardo infarkto etiopatogenezę. Stinga duomenų apie biologinius žymenis, kurie padėtų pagrįsti pokovidinio sindromo esminį poveikį ūminio miokardo infarkto išsivystymui.

The present invention provides a new formulation which comprises Elsholtzia ciliata Extract. Experiments have shown that ECE decreases the rate of depolarization of upstroke of myocardial action potential, slows the propagation of electrical excitation and distributes the ECG QRS range, i.e. treats the heart as a first-class anti-arrhythmic drug. Due to its herbal origin, the ECE can be well tolerated and widely used as a safe drug for eliminating cardiac arrhythmias.

Background and Aims Post-acute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes pandemic coronavirus disease 2019 (COVID-19) leads to cardiovascular problems. It has been demonstrated that COVID-19 increases the levels of intracellular reactive oxygen species in neutrophils to stimulate neutrophil extracellular traps (NETs) formation which contribute DNA burden and thrombosis, including ST-segment elevation myocardial infarction (STEMI). Exonucleases are important in neutralization the harmful effect of NETs excess by degrading the cellular DNA. The aim of this study was to evaluate the role of TREX1 polymorphism and dsDNA in patients with STEMI after the post-acute phase of the COVID-19. Methods A total of 233 patients with STEMI at Hospital of Lithuanian University of Health Sciences were included in the study. From them 117 patients with STEMI had past diagnosis of SARS-CoV-2 infection. Double-stranded DNA (dsDNA) concentrations in plasma were measured with Quant-iT PicoGreen reagent. Single-nucleotide polymorphism (SNP) of the TREX1 (rs11797) were evaluated using real-time PCR with TaqMan SNP Genotyping Assay according to the manufacturer’s instructions. Results CT or TT genotypes of TREX1 were more frequent in STEMI patients with past COVID-19 (72.6 proc. vs 60.3 proc., P = 0.047). dsDNA level did not differ between groups. Univariate logistic regression analysis revealed that patients with past COVID-19 and having CC and CT genotypes were significantly associated with increased odds for MI (OR = 1.746, P = 0.048). Conclusions Our findings demonstrated that TREX1 polymorphism is associated with increased risk for the onset of MI after the post-acute phase of the COVID-19.

Pasaulyje dideliu mastu išplitusios koronavirusinės ligos 2019 (COVID-19) poveikis kiekvieno žmogaus sveikatos būklei yra skirtingas. Dalis COVID-19 persirgusių asmenų yra linkę patirti įvairius nuolatinius ar naujus sveikatos būklės sutrikimus. COVID-19 pandemijos pradžioje nustatyta, kad gretutinėmis ligomis sergantiems ir ūmaus respiracinio sindromo koronavirusu 2 (SARS-CoV-2) užsikrėtusiems pacientams yra didesnė liekamųjų reiškinių rizika [1]. Vienas pagrindinių COVID-19 ligos mechanizmų yra netozė, kai SARS-CoV-2 virusų sunaikinimui neutrofilai išskiria neutrofilų užląstelinį tinklą (NET). Šią tinklą primenančią struktūrą sudaro dvispiralės deoksiribonukleorūgšties (DNR) vijos, histonai ir iš citoplazminių granulių išsiskyrę baltymai. NET yra svarbi įgimto imuniteto dalis kovai su mikroorganizmais, tačiau sutrikusi netozės reguliacija ir NET komponentų perteklius turi įtakos daugeliui patologijų. Sergančiųjų SARS-CoV-2 infekcija ir ūminiu miokardo infarktu (ŪMI) iš vainikinių kraujagyslių aspiruotuose trombuose nustatytos reikšmingai didesnės NET komponentų koncentracijos nei šia infekcija nesirgusių ŪMI pacientų trombuose [2]. Manoma, kad neutrofilų užląstelinis tinklas pasižymi prokoaguliacinėmis savybėmis ir citotoksiškumu kraujagyslių endotelio ląstelėms [3]. Taip pat įrodyta, kad COVID-19 liga persirgusiems pacientams išlieka padidėjusi netozės iniciacija [4]. Netozės reguliacijai ypač svarbios endonukleazės ir egzonukleazės, kurios neutralizuoja NET pertekliaus žalingą poveikį, nes suardo šios struktūros pagrindą sudarančią užląstelinę DNR [5]. Endonukleazių šeima, dar vadinama DNRazėmis. NET struktūrą sudarančią DNR, kuri yra atspari DNRazėms, ardo 3‘-egzonukleazės (TREX1). Tačiau, kai įvyksta genetinės mutacijos nukleazes koduojančiuose genuose, susiformuoja defektyvūs fermentai. Šių fermentų sutrikęs funkcionalumas dažniausiai siejamas su autoimuninėmis ligomis, tačiau nustatytas ryšys tarp sumažėjusio DNRazės 1 aktyvumo dėl DNASE1 geno polimorfizmo ir padidėjusio NET kiekio sergant ŪMI bei sunkesnės ligos eigos [6]. Taip pat nustatytas ryšys tarp TREX1 geno mutacijų ir smulkiųjų kraujagyslių išemijos [7]. Genetiniai pokyčiai, kurie galėtų lemti paūmėjusius arba naujus sveikatos sutrikimus COVID-19 liga persirgusiems asmenims, vis dar nėra nustatyti. Šiame tyrime įvertinome DNASE1 rs1053874 ir TREX1 rs11797 genų VNP reikšmę miokardo infarkto išsivystymui persirgus COVID-19 liga. Šis projektas unikalus tuo, kad nei Lietuvoje, nei užsienio šalyse nebuvo atliktas tokio pobūdžio tyrimas. [...].

Introduction The NR3C2 gene encodes mineralocorticoid receptor (MR) protein, which is responsible for regulating sodium concentration in the body. Lately MR has gained attention, it is considered one of the most important stress-related genes. Currently, no data is available concerning the association of NR3C2 gene polymorphism rs5522 with the events of ST segment elevation myocardial infarction (STEMI) and non-ST segment elevation acute myocardial infarction (NSTEMI). Aim To evaluate the relationship between the genetic polymorphism rs5522 of NR3C2 gene and the event rate of STEMI and NSTEMI. [...].

Pogumburio–posmegeninės liaukos–antinksčių ašies aktyvinimas yra fiziologinis atsakas į stresą, kad išsaugotų homeostazę. Užsitęsus šios ašies aktyvacijai, streso hormonas, kortizolis, tampa žalingas širdies ir kraujagyslių sistemai. Skirtingai nei inkstų epitelinėse ląstelėse, kardiomiocitų mineralkortikoidinių receptorių (MR) ligandas yra ne tik aldosteronas, bet ir kortizolis, kurio tūkstantį kartų yra daugiau širdyje. MR reikšminga įtaka kairiojo skilvelio remodeliavimuisi, aritmijoms atsirasti yra moksliškai pagrįsta ankstesniuose tyrimuose in vitro bei in vivo gyvūnų modeliuose. Tyrimo uždaviniai: nustatyti kortizolio koncentracijos serume, kortizolio indekso ir MR koduojančio geno NR3C2 vieno nukleotido polimorfizmo (VNP) (rs5522, rs5070950, rs4635799) ir jų alelių dažnumų sąsają prognozuojant miokardo infarkto (MI) eigą ir baigtis. Tyrimo metu nustatėme: 1. kortizolio koncentracijos slenkstines vertes prieširdinių ir skilvelinių ritmo sutrikimų bei mirčių prognozėms ŪMI hospitaliniu laikotarpiu; 2. kortizolio indekso slenkstinę vertę ≥100, prognozuojančią mirtį 2 metų laikotarpyje po ŪMI; 3. didesnę tikimybę sirgti MI kai S–T segmentas pakilęs pacientams, turintiems NR3C2 VNP rs5522 izoleucino/izoleucino genotipą, o turintiems rs5522 valino alelį – mažesnę tikimybę įvykti prieširdžių virpėjimui / prieširdžių plazdėjimui ir skilveliniams ritmo sutrikimams ankstyvojoje ŪMI fazėje.

Late-life depression (LLD) is a multifactorial disorder, with susceptibility and vulnerability potentially influenced by gene-environment interaction. The aim of this study was to investigate whether the 5-HTTLPR polymorphism is associated with LLD. The sample of 353 participants aged 65 years and over was randomly selected from the list of Kaunas city inhabitants by Residents' Register Service of Lithuania. Depressive symptoms were ascertained using the EURO-D scale. The List of Threatening Events Questionnaire was used to identify stressful life events that happened over the last 6 months and during lifetime. A 5-HTTLPR and lifetime stressful events interaction was indicated by higher odds of depression in those with s/s genotype who experienced high stress compared to l/l carriers with low or medium stress, while 5-HTTLPR and current stressful events interaction analysis revealed that carriers of either one or two copies of the s allele had increased odds of depressive symptoms associated with stress compared to participants with the l/l genotype not exposed to stressful situations. Although no significant direct association was found between the 5-HTTLPR short allele and depression, our findings demonstrated that lifetime or current stressful life events and their modification by 5-HTTLPR genotype are risk factors for late-life depression.

Introduction: Patients with acute myocardial infarction (AMI) suffer from distress that causes a rise in stress hormone (cortisol), which acts through glucocorticoid receptors (GR) and mineralocorticoid receptors (MR). Both receptors are present in cardiomyocyte nuclei (1–4). MR are encoded by the human gene NR3C2 (nuclear receptor subfamily 3 group C member (–-6). Evidence has shown that the MR in cardiac tissue are vital for the cardiac remodelling that starts right after suffering AMI (7). We hypothesised that NR3C2 gene associates with ventricular remodelling and possibly reduces harmful effects of cortisol on cardiomyocytes Aim:The aim is to evaluate the impact of the NR3C2 rs2070950, rs4635799 andrs5522 genes polymorphism on left ventricular (LV) remodeling in AMI patients. Methods: Study included 127 patients treated at our university of health sciences hospital after suffering from AMI; all study subjects underwent primary percutaneous coronary intervention (PCI) and guideline-directed medical treatment (1). Single-nucleotide polymorphisms (SNP) of NR3C2 gene (rs5522, rs4635799, rs2070950) were evaluated using real-time PCR. All patients had echocardiography done 72 hours after admission and at 6 month follow up. Based on the change in LV end – diastolic volume (LVEDV), end –systolic volume (LVESV) and LV ejection fraction (LVEF) four functional left ventricular remodelling groups (FLVR) were defined: Group 1 – EDV<20% and the same or increased LVEF, Group 2 – EDV<20% and a decrease of LVEF, Group 3 – EDV≥20% and the same or increased LVEF, group 4 – EDV≥20% and decreased LVEF(8). NR3C2 gene polymorphism were analysed using the exact Fisher’s test. All the statistical analyses were performed with SPSS 27.0 software. The value of p<0.05was considered statistically significant.Results:Risk factors as diabetes mellitus, hypertension, dyslipidemia did not differ across all four groups. Yet in fourth FLVR group there were more smokers, and patients that had higher glucose levels on admission. (Table 1)In the first FLVR group, majority were carrying the rs2070950 GG genotype afterMI, while no patients were carrying the GG genotype in the second and the fourth FLAVOR groups (p<0.05). Furthermore, fourth FLVR group patients after suffering MI more frequently had the rs2070950 C allele than in the first, and the C allele was found more frequently in the second group than in the first and third. (p<0.05).When analyzing the rs4635799, TT genotype was carried more by patients in the first FLVR group than in the second, and in fourth group patients were not carrying the TT genotype at all (p<0.05). The C allele was detected more frequently in the second FLVR group than in the first one (p<0.05). (Table 2) This study showed that the NR3C2 rs2070950 GG genotype and rs4635799 TT genotype protects left ventricle (LV) systolic function of which reduction was associated with the worst prognosis in AMI patients.