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Article ; Online: Effect of pharmacological selectivity of SGLT2 inhibitors on cardiovascular outcomes in patients with type 2 diabetes: a meta-analysis.

Sayour, Alex Ali / Oláh, Attila / Ruppert, Mihály / Barta, Bálint András / Merkely, Béla / Radovits, Tamás

2024 Volume 14, Issue 1, Page(s) 2188

Abstract: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce major adverse cardiovascular events (MACE) in type 2 diabetic (T2DM) patients. Pharmacological selectivity of these agents to SGLT2 over SGLT1 is highly variant, with unknown clinical relevance. ... ...

Abstract	Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce major adverse cardiovascular events (MACE) in type 2 diabetic (T2DM) patients. Pharmacological selectivity of these agents to SGLT2 over SGLT1 is highly variant, with unknown clinical relevance. Genetically reduced SGLT1-but not SGLT2-activity correlates with lower risk of heart failure and mortality, therefore additional non-selective SGLT1 inhibition might be beneficial. In this prespecified meta-analysis, we included 6 randomized, placebo-controlled cardiovascular outcome trials of SGLT2 inhibitors assessing MACE in 57,553 patients with T2DM. Mixed-effects meta-regression revealed that pharmacological selectivity of SGLT2 inhibitors (either as continuous or dichotomized variable) had no significant impact on most outcomes. However, lower SGLT2 selectivity correlated with significantly lower risk of stroke (pseudo-R
MeSH term(s)	Humans ; Diabetes Mellitus, Type 2/complications ; Diabetes Mellitus, Type 2/drug therapy ; Diabetes Mellitus, Type 2/chemically induced ; Sodium-Glucose Transporter 2 Inhibitors/adverse effects ; Hypoglycemic Agents/adverse effects ; Sodium-Glucose Transporter 2 ; Stroke/drug therapy
Chemical Substances	Sodium-Glucose Transporter 2 Inhibitors ; Hypoglycemic Agents ; Sodium-Glucose Transporter 2
Language	English
Publishing date	2024-01-25
Publishing country	England
Document type	Meta-Analysis ; Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-52331-w
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Article ; Online: mRNA-LNP COVID-19 Vaccine Lipids Induce Complement Activation and Production of Proinflammatory Cytokines: Mechanisms, Effects of Complement Inhibitors, and Relevance to Adverse Reactions.

Bakos, Tamás / Mészáros, Tamás / Kozma, Gergely Tibor / Berényi, Petra / Facskó, Réka / Farkas, Henriette / Dézsi, László / Heirman, Carlo / de Koker, Stefaan / Schiffelers, Raymond / Glatter, Kathryn Anne / Radovits, Tamás / Szénási, Gábor / Szebeni, János

International journal of molecular sciences

2024 Volume 25, Issue 7

Abstract: A small fraction of people vaccinated with mRNA-lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these ... ...

Abstract	A small fraction of people vaccinated with mRNA-lipid nanoparticle (mRNA-LNP)-based COVID-19 vaccines display acute or subacute inflammatory symptoms whose mechanism has not been clarified to date. To better understand the molecular mechanism of these adverse events (AEs), here, we analyzed in vitro the vaccine-induced induction and interrelations of the following two major inflammatory processes: complement (C) activation and release of proinflammatory cytokines. Incubation of Pfizer-BioNTech's Comirnaty and Moderna's Spikevax with 75% human serum led to significant increases in C5a, sC5b-9, and Bb but not C4d, indicating C activation mainly via the alternative pathway. Control PEGylated liposomes (Doxebo) also induced C activation, but, on a weight basis, it was ~5 times less effective than that of Comirnaty. Viral or synthetic naked mRNAs had no C-activating effects. In peripheral blood mononuclear cell (PBMC) cultures supplemented with 20% autologous serum, besides C activation, Comirnaty induced the secretion of proinflammatory cytokines in the following order: IL-1α < IFN-γ < IL-1β < TNF-α < IL-6 < IL-8. Heat-inactivation of C in serum prevented a rise in IL-1α, IL-1β, and TNF-α, suggesting C-dependence of these cytokines' induction, although the C5 blocker Soliris and C1 inhibitor Berinert, which effectively inhibited C activation in both systems, did not suppress the release of any cytokines. These findings suggest that the inflammatory AEs of mRNA-LNP vaccines are due, at least in part, to stimulation of both arms of the innate immune system, whereupon C activation may be causally involved in the induction of some, but not all, inflammatory cytokines. Thus, the pharmacological attenuation of inflammatory AEs may not be achieved via monotherapy with the tested C inhibitors; efficacy may require combination therapy with different C inhibitors and/or other anti-inflammatory agents.
MeSH term(s)	Humans ; Complement Inactivating Agents ; Liposomes ; COVID-19 Vaccines/adverse effects ; Leukocytes, Mononuclear ; Cytokines ; Tumor Necrosis Factor-alpha ; BNT162 Vaccine ; COVID-19 ; Complement Activation ; Lipids ; Nanoparticles
Chemical Substances	Complement Inactivating Agents ; Lipid Nanoparticles ; Liposomes ; COVID-19 Vaccines ; Cytokines ; Tumor Necrosis Factor-alpha ; BNT162 Vaccine ; Lipids
Language	English
Publishing date	2024-03-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25073595
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Article ; Online: Orthostasis Is Impaired Due to Fatiguing Intensive Acute Concentric Exercise Succeeded by Isometric Weight-Loaded Wall-Sit in Delayed-Onset Muscle Soreness: A Pilot Study.

Sonkodi, Balázs / Radovits, Tamás / Csulak, Emese / Kopper, Bence / Sydó, Nóra / Merkely, Béla

Sports (Basel, Switzerland)

2023 Volume 11, Issue 11

Abstract: The aim of the study was to investigate any indication of diminished orthostatic tolerance as a result of fatiguing intensive acute concentric exercise with a successive isometric wall-sit followed by an orthostatic stress test, with a special focus on ... ...

Abstract	The aim of the study was to investigate any indication of diminished orthostatic tolerance as a result of fatiguing intensive acute concentric exercise with a successive isometric wall-sit followed by an orthostatic stress test, with a special focus on any distinguishable alterations due to a delayed-onset muscle soreness effect. The exercise protocol was carried out among nineteen (10 female, 9 male) junior swimmers from the Hungarian National Swim Team. All athletes showed a positive orthostatic stress test right after our exercise protocol. The diastolic blood pressure was significantly lower due to the delayed-onset muscle soreness effect in the standing position after the supine position of the orthostatic stress test, in contrast to the athletes who did not experience delayed-onset muscle soreness. Furthermore, the heart rate was dysregulated in athletes with a delayed-onset muscle soreness effect when they assumed a supine position after the sustained standing position during the orthostatic stress test, in contrast to the athletes without delayed-onset muscle soreness. Interesting to note is that, in three subjects, the sustained standing position decreased the heart rate below the level of the initial supine position and six athletes experienced dizziness in the standing position, and all of these athletes were from the group that experienced delayed-onset muscle soreness. Accordingly, this study, for the first time, demonstrated that delayed-onset muscle soreness impairs orthostasis after unaccustomed fatiguing intensive acute concentric exercise with a successive isometric weight-loaded wall-sit; however, validation of this association should be investigated in a larger sample size.
Language	English
Publishing date	2023-10-27
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2704239-X
ISSN	2075-4663 ; 2075-4663
ISSN (online)	2075-4663
ISSN	2075-4663
DOI	10.3390/sports11110209
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Article ; Online: NASH triggers cardiometabolic HFpEF in aging mice.

Kucsera, Dániel / Ruppert, Mihály / Sayour, Nabil V / Tóth, Viktória E / Kovács, Tamás / Hegedűs, Zsombor I / Onódi, Zsófia / Fábián, Alexandra / Kovács, Attila / Radovits, Tamás / Merkely, Béla / Pacher, Pál / Ferdinandy, Péter / Varga, Zoltán V

GeroScience

2024

Abstract: Both heart failure with preserved ejection fraction (HFpEF) and non-alcoholic fatty liver disease (NAFLD) develop due to metabolic dysregulation, has similar risk factors (e.g., insulin resistance, systemic inflammation) and are unresolved clinical ... ...

Abstract	Both heart failure with preserved ejection fraction (HFpEF) and non-alcoholic fatty liver disease (NAFLD) develop due to metabolic dysregulation, has similar risk factors (e.g., insulin resistance, systemic inflammation) and are unresolved clinical challenges. Therefore, the potential link between the two disease is important to study. We aimed to evaluate whether NASH is an independent factor of cardiac dysfunction and to investigate the age dependent effects of NASH on cardiac function. C57Bl/6 J middle aged (10 months old) and aged mice (24 months old) were fed either control or choline deficient (CDAA) diet for 8 weeks. Before termination, echocardiography was performed. Upon termination, organ samples were isolated for histological and molecular analysis. CDAA diet led to the development of NASH in both age groups, without inducing weight gain, allowing to study the direct effect of NASH on cardiac function. Mice with NASH developed hepatomegaly, fibrosis, and inflammation. Aged animals had increased heart weight. Conventional echocardiography revealed normal systolic function in all cohorts, while increased left ventricular volumes in aged mice. Two-dimensional speckle tracking echocardiography showed subtle systolic and diastolic deterioration in aged mice with NASH. Histologic analyses of cardiac samples showed increased cross-sectional area, pronounced fibrosis and Col1a1 gene expression, and elevated intracardiac CD68
Language	English
Publishing date	2024-04-17
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2886586-8
ISSN	2509-2723 ; 2509-2715
ISSN (online)	2509-2723
ISSN	2509-2715
DOI	10.1007/s11357-024-01153-9
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Article ; Online: Zymosan Particle-Induced Hemodynamic, Cytokine and Blood Cell Changes in Pigs: An Innate Immune Stimulation Model with Relevance to Cytokine Storm Syndrome and Severe COVID-19.

Kökény, Gábor / Bakos, Tamás / Barta, Bálint András / Nagy, Georgina Viktória / Mészáros, Tamás / Kozma, Gergely T / Szabó, András / Szebeni, János / Merkely, Béla / Radovits, Tamás

International journal of molecular sciences

2023 Volume 24, Issue 2

Abstract: Hemodynamic disturbance, a rise in neutrophil-to-lymphocyte ratio (NLR) and release of inflammatory cytokines into blood, is a bad prognostic indicator in severe COVID-19 and other diseases involving cytokine storm syndrome (CSS). The purpose of this ... ...

Abstract	Hemodynamic disturbance, a rise in neutrophil-to-lymphocyte ratio (NLR) and release of inflammatory cytokines into blood, is a bad prognostic indicator in severe COVID-19 and other diseases involving cytokine storm syndrome (CSS). The purpose of this study was to explore if zymosan, a known stimulator of the innate immune system, could reproduce these changes in pigs. Pigs were instrumented for hemodynamic analysis and, after i.v. administration of zymosan, serial blood samples were taken to measure blood cell changes, cytokine gene transcription in PBMC and blood levels of inflammatory cytokines, using qPCR and ELISA. Zymosan bolus (0.1 mg/kg) elicited transient hemodynamic disturbance within minutes without detectable cytokine or blood cell changes. In contrast, infusion of 1 mg/kg zymosan triggered maximal pulmonary hypertension with tachycardia, lasting for 30 min. This was followed by a transient granulopenia and then, up to 6 h, major granulocytosis, resulting in a 3-4-fold increase in NLR. These changes were paralleled by massive transcription and/or rise in IL-6, TNF-alpha, CCL-2, CXCL-10, and IL-1RA in blood. There was significant correlation between lymphopenia and IL-6 gene expression. We conclude that the presented model may enable mechanistic studies on late-stage COVID-19 and CSS, as well as streamlined drug testing against these conditions.
MeSH term(s)	Swine ; Animals ; Cytokines/metabolism ; Zymosan/pharmacology ; Interleukin-6/metabolism ; COVID-19 ; Cytokine Release Syndrome/etiology ; Leukocytes, Mononuclear/metabolism ; Immunity, Innate
Chemical Substances	Cytokines ; Zymosan (9010-72-4) ; Interleukin-6
Language	English
Publishing date	2023-01-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms24021138
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Article ; Online: IL-1β neutralization prevents diastolic dysfunction development, but lacks hepatoprotective effect in an aged mouse model of NASH.

Kucsera, Dániel / Tóth, Viktória E / Sayour, Nabil V / Kovács, Tamás / Gergely, Tamás G / Ruppert, Mihály / Radovits, Tamás / Fábián, Alexandra / Kovács, Attila / Merkely, Béla / Ferdinandy, Péter / Varga, Zoltán V

Scientific reports

2023 Volume 13, Issue 1, Page(s) 356

Abstract: Interleukin-1β (IL-1β) is a key mediator of non-alcoholic steatohepatitis (NASH), a chronic liver disease, and of systemic inflammation-driven aging. IL-1β contributes to cardio-metabolic decline, and may promote hepatic oncogenic transformation. ... ...

Abstract	Interleukin-1β (IL-1β) is a key mediator of non-alcoholic steatohepatitis (NASH), a chronic liver disease, and of systemic inflammation-driven aging. IL-1β contributes to cardio-metabolic decline, and may promote hepatic oncogenic transformation. Therefore, IL-1β is a potential therapeutic target in these pathologies. We aimed to investigate the hepatic and cardiac effects of an IL-1β targeting monoclonal antibody in an aged mouse model of NASH. 24 months old male C57Bl/6J mice were fed with control or choline deficient (CDAA) diet and were treated with isotype control or anti-IL-1β Mab for 8 weeks. Cardiac functions were assessed by conventional-and 2D speckle tracking echocardiography. Liver samples were analyzed by immunohistochemistry and qRT-PCR. Echocardiography revealed improved cardiac diastolic function in anti-IL-1β treated mice with NASH. Marked hepatic fibrosis developed in CDAA-fed group, but IL-1β inhibition affected fibrosis only at transcriptomic level. Hepatic inflammation was not affected by the IL-1β inhibitor. PCNA staining revealed intensive hepatocyte proliferation in CDAA-fed animals, which was not influenced by neutralization of IL-1β. IL-1β inhibition increased hepatic expression of Pd-1 and Ctla4, while Pd-l1 expression increased in NASH. In conclusion, IL-1β inhibition improved cardiac diastolic function, but did not ameliorate features of NASH; moreover, even promoted hepatic immune checkpoint expression, with concomitant NASH-related hepatocellular proliferation.
MeSH term(s)	Male ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/pathology ; Interleukin-1beta/metabolism ; Liver/metabolism ; Liver Cirrhosis/pathology ; Disease Models, Animal ; Fibrosis ; Mice, Inbred C57BL
Chemical Substances	Interleukin-1beta ; CDAA (93-71-0)
Language	English
Publishing date	2023-01-07
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-26896-3
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Article ; Online: Role of anti-polyethylene glycol (PEG) antibodies in the allergic reactions to PEG-containing Covid-19 vaccines: Evidence for immunogenicity of PEG.

Kozma, Gergely Tibor / Mészáros, Tamás / Berényi, Petra / Facskó, Réka / Patkó, Zsófia / Oláh, Csaba Zs / Nagy, Adrienne / Fülöp, Tamás Gyula / Glatter, Kathryn Anne / Radovits, Tamás / Merkely, Béla / Szebeni, János

Vaccine

2023 Volume 41, Issue 31, Page(s) 4561–4570

Abstract: A small fraction of recipients who receive polyethylene-glycol (PEG)-containing COVID-19 mRNA-LNP vaccines (Comirnaty and Spikevax) develop hypersensitivity reactions (HSRs) or anaphylaxis. A causal role of anti-PEG antibodies (Abs) has been proposed, ... ...

Abstract	A small fraction of recipients who receive polyethylene-glycol (PEG)-containing COVID-19 mRNA-LNP vaccines (Comirnaty and Spikevax) develop hypersensitivity reactions (HSRs) or anaphylaxis. A causal role of anti-PEG antibodies (Abs) has been proposed, but not yet been proven in humans.We used ELISA for serial measurements of SARS-CoV-2 neutralizing Ab (anti-S) and anti-PEG IgG/IgM Ab levels before and after the first and subsequent booster vaccinations with mRNA-LNP vaccines in a total of 291 blood donors. The HSRs in 15 subjects were graded and correlated with anti-PEG IgG/IgM, just as the anti-S and anti-PEG Ab levels with each other. The impacts of gender, allergy, mastocytosis and use of cosmetics were also analyzed. Serial testing of two or more plasma samples showed substantial individual variation of anti-S Ab levels after repeated vaccinations, just as the levels of anti-PEG IgG and IgM, which were over baseline in 98-99 % of unvaccinated individuals. About 3-4 % of subjects in the strongly left-skewed distribution had 15-45-fold higher values than the median, referred to as anti-PEG Ab supercarriers. Both vaccines caused significant rises of anti-PEG IgG/IgM with >10-fold rises in about ∼10 % of Comirnaty, and all Spikevax recipients. The anti-PEG IgG and/or IgM levels in the 15 vaccine reactors (3 anaphylaxis) were significantly higher compared to nonreactors. Serial testing of plasma showed significant correlation between the booster injection-induced rises of anti-S and anti-PEG IgGs, suggesting coupled anti-S and anti-PEG immunogenicity.Conclusions: The small percentage of people who have extremelevels of anti-PEG Ab in their blood may be at increased risk for HSRs/anaphylaxis to PEGylated vaccines and other PEGylated injectables. This risk might be further increased by the anti-PEG immunogenicity of these vaccines. Screening for anti-PEG Ab "supercarriers" may help predicting reactors and thus preventing these adverse phenomena.
MeSH term(s)	Humans ; 2019-nCoV Vaccine mRNA-1273 ; Anaphylaxis ; BNT162 Vaccine ; COVID-19/prevention & control ; COVID-19 Vaccines/adverse effects ; Glycols ; Immunoglobulin G ; Immunoglobulin M ; RNA, Messenger ; SARS-CoV-2
Chemical Substances	2019-nCoV Vaccine mRNA-1273 (EPK39PL4R4) ; BNT162 Vaccine ; COVID-19 Vaccines ; Glycols ; Immunoglobulin G ; Immunoglobulin M ; RNA, Messenger
Language	English
Publishing date	2023-06-05
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	605674-x
ISSN	1873-2518 ; 0264-410X
ISSN (online)	1873-2518
ISSN	0264-410X
DOI	10.1016/j.vaccine.2023.06.009
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Zs.MO 458: Show issues

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Article ; Online: mRNA-LNP COVID-19 vaccine lipids induce low level complement activation and production of proinflammatory cytokines: Mechanisms, effects of complement inhibitors, and relevance to adverse reactions

bioRxiv

Abstract: Messenger RNA-containing lipid nanoparticles (mRNA-LNPs) enabled widespread COVID-19 vaccination with a small fraction of vaccine recipients displaying acute or sub-acute inflammatory symptoms. The molecular mechanism of these adverse events (AEs) ... ...

Abstract	Messenger RNA-containing lipid nanoparticles (mRNA-LNPs) enabled widespread COVID-19 vaccination with a small fraction of vaccine recipients displaying acute or sub-acute inflammatory symptoms. The molecular mechanism of these adverse events (AEs) remains undetermined. Here we report that the mRNA-LNP vaccine, Comirnaty, triggers low-level complement (C) activation and production of inflammatory cytokines, which may be key underlying processes of inflammatory AEs. In serum, Comirnaty and the control PEGylated liposome (Doxebo) caused different rises of C split products, C5a, sC5b-9, Bb and C4d, indicating stimulation of the classical pathway of C activation mainly by the liposomes, while a stronger stimulation of the alternative pathway was equal with the vaccine and the liposomes. Spikevax had similar C activation as Comirnaty, but viral or synthetic mRNAs had no such effect. In autologous serum-supplemented peripheral blood mononuclear cell (PBMC) cultures, Comirnaty caused increases in the levels of sC5b-9 and proinflammatory cytokines in the following order: IL-1α < IFN-γ < IL-1β < TNF-α < IL-6 < IL-8, whereas heat-inactivation of serum prevented the rises of IL-1α, IL-1β, and TNF-α. Clinical C inhibitors, Soliris and Berinert, suppressed vaccine-induced C activation in serum but did not affect cytokine production when applied individually. These findings suggest that the PEGylated lipid coating of mRNA-LNP nanoparticles can trigger C activation mainly via the alternative pathway, which may be causally related to the induction of some, but not all inflammatory cytokines. While innate immune stimulation is essential for the vaccine9s efficacy, concurrent production of C- and PBMC-derived inflammatory mediators may contribute to some of the AEs. Pharmacological attenuation of harmful cytokine production using C inhibitors likely requires blocking the C cascade at multiple points.
Keywords	covid19
Language	English
Publishing date	2024-01-15
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2024.01.12.575122
Database	COVID19

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Article: Zinc-aspirin preconditioning reduces endothelial damage of arterial grafts in a rodent model of revascularization.

Benke, Kálmán / Stengl, Roland / Stark, Klára Aliz / Bai, Yang / Radovits, Tamás / Loganathan, Sivakkanan / Korkmaz-Icöz, Sevil / Csonka, Máté / Karck, Matthias / Szabó, Gábor / Veres, Gábor

Frontiers in cardiovascular medicine

2024 Volume 10, Page(s) 1288128

Abstract: Introduction: Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure. The prognosis of revascularization via CABG is determined by the patency of the used grafts, for which an intact endothelium is essential. The degree of ... ...

Abstract	Introduction: Coronary artery bypass grafting (CABG) is the most common cardiac surgical procedure. The prognosis of revascularization via CABG is determined by the patency of the used grafts, for which an intact endothelium is essential. The degree of ischemia-reperfusion injury (IRI), which occurs during the harvest and implantation of the grafts, is an important determinant of graft patency. Preconditioning with aspirin, a nonsteroidal anti-inflammatory drug has been shown to reduce the functional and molecular damage of arterial grafts in a rodent model. Studies have found that the zinc-aspirin complex may be able to exert an even better protective effect in pathological cardiovascular conditions. Thus, our aim was to characterize the protective effect of zinc-aspirin complex on free arterial grafts in a rodent model of revascularization. Methods: Donor Lewis rats were treated with either zinc-aspirin, aspirin, or placebo ( Results: The endothelium dependent maximal vasorelaxation was improved (non-transplanted control group: 82% ± 3%, transplanted control group: 14% ± 2%, aspirin group: 31% ± 4%, zinc-aspirin group: 52% ± 4%), the nitro-oxidative stress and cell apoptosis decreased, and significant endothelial protection was shown in the groups preconditioned with aspirin or zinc-aspirin. However, zinc-aspirin proved to be more effective in the reduction of IRI, than aspirin alone. Discussion: Preconditioning with zinc-aspirin could be a promising way to protect the function and structural integrity of free arterial grafts, thus improving the outcomes of CABG.
Language	English
Publishing date	2024-01-04
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2781496-8
ISSN	2297-055X
ISSN	2297-055X
DOI	10.3389/fcvm.2023.1288128
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Article ; Online: Recipient Pericardial Apolipoprotein Levels Might Be an Indicator of Worse Outcomes after Orthotopic Heart Transplantation.

Székely, Andrea / Pállinger, Éva / Töreki, Evelin / Ifju, Mandula / Barta, Bálint András / Szécsi, Balázs / Losoncz, Eszter / Dohy, Zsófia / Barabás, Imre János / Kosztin, Annamária / Buzas, Edit I / Radovits, Tamás / Merkely, Béla

International journal of molecular sciences

2024 Volume 25, Issue 3

Abstract: Background: End-stage heart failure (ESHF) leads to hypoperfusion and edema formation throughout the body and is accompanied by neurohormonal and immunological alterations. Orthotopic heart transplantation (HTX) has been used as a beneficial option for ... ...

Abstract	Background: End-stage heart failure (ESHF) leads to hypoperfusion and edema formation throughout the body and is accompanied by neurohormonal and immunological alterations. Orthotopic heart transplantation (HTX) has been used as a beneficial option for ESHF. Due to the shortage of donor hearts, the ideal matching and timing of donors and recipients has become more important. Purpose: In this study, our aim was to explore the relationship between the clinical outcomes of HTX and the cytokine and apolipoprotein profiles of the recipient pericardial fluid obtained at heart transplantation after opening the pericardial sac. Materials and methods: The clinical data and the interleukin, adipokine, and lipoprotein levels in the pericardial fluid of twenty HTX recipients were investigated. Outcome variables included primer graft dysfunction (PGD), the need for post-transplantation mechanical cardiac support (MCS), International Society for Heart and Lung Transplantation grade ≥2R rejection, and mortality. Recipient risk scores were also investigated. Results: Leptin levels were significantly lower in patients with PGD than in those without PGD (median: 6.36 (IQR: 5.55-6.62) versus 7.54 (IQR = 6.71-10.44); Conclusion: Our results indicate that apolipoproteins can facilitate the monitoring of rejection and could be a useful tool in the forecasting of early and late complications.
MeSH term(s)	Humans ; Heart Transplantation/adverse effects ; Heart Transplantation/methods ; Tissue Donors ; Lung Transplantation ; Risk Factors ; Apolipoproteins ; Retrospective Studies ; Graft Rejection/etiology
Chemical Substances	Apolipoproteins
Language	English
Publishing date	2024-02-01
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms25031752
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