Investigating prenatal hypoxia is difficult in mammals, as there are confounding factors stemming from maternal adaptations and compensatory mechanisms. We have thus established an avian model of hypoxic incubation (starting after 2 days of normoxia, 15% O2, normobaric, until the time of sampling at embryonic day 8) to study embryonic reactions to low oxygen concentration. Our previous studies have shown increased vascularization, oedema, and ventricular wall thinning preceding the lethality at mid-gestation. Analysis of the cardiac proteome after 6 days of hypoxic incubation showed strong upregulation of enzymes involved in anaerobic glycolysis as well as an increase in apoptosis-related proteins, cell adhesion proteins, and secretory activity.
- Klíčová slova
- Chick embryo, Glycolysis, Heart, Hypoxia, Metabolism, Proteomics,
- MeSH
- apoptóza MeSH
- glykolýza MeSH
- hypoxie * metabolismus MeSH
- kuřecí embryo MeSH
- myokard metabolismus MeSH
- proteom metabolismus MeSH
- proteomika * metody MeSH
- srdce * embryologie MeSH
- zvířata MeSH
- Check Tag
- kuřecí embryo MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- proteom MeSH
Myocardial dysfunction, characterized by impaired cardiac muscle function, arises from diverse etiologies, including coronary artery disease, myocardial infarction, cardiomyopathies, hypertension, and valvular heart disease. Recent advancements have highlighted the roles of exosomes and non-coding RNAs in the pathophysiology of myocardial dysfunction. Exosomes are small extracellular vesicles released by cardiac and other cells that facilitate intercellular communication through their molecular cargo, including ncRNAs. ncRNAs are known to play critical roles in gene regulation through diverse mechanisms, impacting oxidative stress, fibrosis, and other factors associated with myocardial dysfunction. Dysregulation of these molecules correlates with disease progression, presenting opportunities for therapeutic interventions. This review explores the mechanistic interplay between exosomes and ncRNAs, underscoring their potential as biomarkers and therapeutic agents in myocardial dysfunction. Emerging evidence supports the use of engineered exosomes and modified ncRNAs to enhance cardiac repair by targeting signaling pathways associated with fibrosis, apoptosis, and angiogenesis. Despite promising preclinical results, delivery, stability, and immunogenicity challenges remain. Further research is needed to optimize clinical translation. Understanding these intricate mechanisms may drive the development of innovative strategies for diagnosing and treating myocardial dysfunction, ultimately improving patient outcomes.
- Klíčová slova
- Bioengineering, Cardiomyopathies, Exosomes, Myocardial dysfunction, Non-coding RNAs,
- MeSH
- biologické markery metabolismus MeSH
- exozómy * metabolismus genetika MeSH
- fibróza MeSH
- kardiomyopatie genetika patofyziologie metabolismus MeSH
- lidé MeSH
- myokard metabolismus patologie MeSH
- nekódující RNA * genetika MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- biologické markery MeSH
- nekódující RNA * MeSH
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been associated with significant cardiovascular complications, including myocardial infection and pulmonary embolism. This study aims to elucidate the relationship between the presence of SARS-CoV-2 RNA in the myocardium of the left ventricle and the levels of IgG and IgM antibodies against the SARS-CoV-2 virus in deceased COVID-19 patients. We conducted a post-mortem examination on 91 individuals who succumbed to COVID-19-related complications. The presence of SARS-CoV-2 RNA in the myocardium of the left ventricle was analyzed reverse transcription real time PCR (RT-qPCR) (EliGene® COVID19 UKV/SAV RT kit, Elisabeth Pharmacon), and antibody levels in serum were analyzed by serological assays (VIDAS SARS-COV-2 IgM and VIDAS SARS-COV-2 IgG II tests, BioMérieux). Of the heart tissue samples, 44 % tested positive for SARS-CoV-2 RNA. Our findings indicate that any detectable level of IgG antibodies against SARS-CoV-2 reduces the risk of viral penetration into the myocardium by more than fourfold. Specifically, individuals with detectable levels of IgG and IgM antibodies exhibited a significantly reduced presence of SARS-CoV-2 RNA in cardiac tissues (p<0.0001 for IgG and p<0.001 for IgM). Notably, all patients who died from pulmonary embolism had elevated levels of IgG antibodies. The study underscores the protective role of IgG and IgM antibodies in preventing SARS-CoV-2 penetration into cardiac tissues. However, high antibody titers were associated with fatal outcomes such as pulmonary embolism, pointing to the intricate balance of immune response in COVID-19 pathology. Key words SARS-CoV-2, Antibody, IgG, IgM, Cardiac damage, qPCR, Pneumonia, Pulmonary embolism, Heart failure.
- MeSH
- COVID-19 * imunologie virologie MeSH
- dospělí MeSH
- imunoglobulin G * krev MeSH
- imunoglobulin M * krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- myokard * imunologie metabolismus MeSH
- protilátky virové * krev MeSH
- RNA virová krev MeSH
- SARS-CoV-2 * imunologie MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- imunoglobulin G * MeSH
- imunoglobulin M * MeSH
- protilátky virové * MeSH
- RNA virová MeSH
The global COVID-19 pandemic, caused by SARS-CoV-2, has led to significant morbidity and mortality, with a profound impact on cardiovascular health. This review investigates the mechanisms of SARS-CoV-2's interaction with cardiac tissue, particularly emphasizing the role of the Spike protein and ACE2 receptor in facilitating viral entry and subsequent cardiac complications. We dissect the structural features of the virus, its interactions with host cell receptors, and the resulting pathophysiological changes in the heart. Highlighting SARS-CoV-2's broad organ tropism, especially its effects on cardiomyocytes via ACE2 and TMPRSS2, the review addresses how these interactions exacerbate cardiovascular issues in patients with pre-existing conditions such as diabetes and hypertension. Additionally, we assess both direct and indirect mechanisms of virus-induced cardiac damage, including myocarditis, arrhythmias, and long-term complications such as 'long COVID'. This review underscores the complexity of SARS-CoV-2's impact on the heart, emphasizing the need for ongoing research to fully understand its long-term effects on cardiovascular health. Key words: COVID-19, Heart, ACE2, Spike protein, Cardiomyocytes, Myocarditis, Long COVID.
- MeSH
- angiotensin-konvertující enzym 2 * metabolismus MeSH
- COVID-19 * metabolismus MeSH
- glykoprotein S, koronavirus * metabolismus MeSH
- internalizace viru MeSH
- kardiomyocyty metabolismus virologie patologie MeSH
- lidé MeSH
- myokard metabolismus patologie MeSH
- SARS-CoV-2 * patogenita MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- ACE2 protein, human MeSH Prohlížeč
- angiotensin-konvertující enzym 2 * MeSH
- glykoprotein S, koronavirus * MeSH
- spike protein, SARS-CoV-2 MeSH Prohlížeč
Experimental and clinical studies have clearly demonstrated significant sex differences in myocardial structure and function, both under physiological and pathological conditions. The best example are significant sex differences in the cardiac tolerance to ischemia/reperfusion injury: pre-menopausal adult female hearts are more resistant as compared to the male myocardium. The importance of these findings is supported by the fact that the number of studies dealing with this issue increased significantly in recent years. Detailed molecular and cellular mechanisms responsible for sex differences are yet to be elucidated; however, it has been stressed that the differences cannot be explained only by the effect of estrogens. In recent years, a promising new hypothesis has been developed, suggesting that mitochondria may play a significant role in the sex differences in cardiac tolerance to oxygen deprivation. However, one is clear already today: sex differences are so important that they should be taken into consideration in the clinical practice for the selection of the optimal diagnostic and therapeutic strategy in the treatment of ischemic heart disease. The present review attempts to summarize the progress in cardiovascular research on sex-related differences in cardiac tolerance to oxygen deprivation during the last 40 years, i.e. from the first experimental observation. Particular attention was paid to the sex-related differences of the normal heart, sex-dependent tolerance to ischemia-reperfusion injury, the role of hormones and, finally, to the possible role of cardiac mitochondria in the mechanism of sex-dependent differences in cardiac tolerance to ischemia/reperfusion injury. Key words: Female heart, Cardiac hypoxic tolerance, Ischemia-reperfusion injury, Sex differences.
- MeSH
- kyslík metabolismus MeSH
- lidé MeSH
- myokard metabolismus patologie MeSH
- pohlavní dimorfismus * MeSH
- reperfuzní poškození myokardu metabolismus patofyziologie MeSH
- sexuální faktory MeSH
- srdeční mitochondrie metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- kyslík MeSH
Cardiac myosin-specific (MyHC) T cells drive the disease pathogenesis of immune checkpoint inhibitor-associated myocarditis (ICI-myocarditis). To determine whether MyHC T cells are tissue-resident memory T (TRM) cells, we characterized cardiac TRM cells in naive mice and established that they have a distinct phenotypic and transcriptional profile that can be defined by their upregulation of CD69, PD-1, and CXCR6. We then investigated the effects of cardiac injury through a modified experimental autoimmune myocarditis mouse model and an ischemia-reperfusion injury mouse model and determined that cardiac inflammation induces the recruitment of autoreactive MyHC TRM cells, which coexpress PD-1 and CD69. To investigate whether the recruited MyHC TRM cells could increase susceptibility to ICI-myocarditis, we developed a two-hit ICI-myocarditis mouse model where cardiac injury was induced, mice were allowed to recover, and then were treated with anti-PD-1 antibodies. We determined that mice who recover from cardiac injury are more susceptible to ICI-myocarditis development. We found that murine and human TRM cells share a similar location in the heart and aggregate along the perimyocardium. We phenotyped cells obtained from pericardial fluid from patients diagnosed with dilated cardiomyopathy and ischemic cardiomyopathy and established that pericardial T cells are predominantly CD69+ TRM cells that up-regulate PD-1. Finally, we determined that human pericardial macrophages produce IL-15, which supports and maintains pericardial TRM cells.
- Klíčová slova
- ICI-myocarditis, PD-1, cardiac immunology, tissue-resident memory T cells,
- MeSH
- antigeny CD279 metabolismus MeSH
- CD antigeny MeSH
- diferenciační antigeny T-lymfocytů metabolismus imunologie MeSH
- inhibitory kontrolních bodů * farmakologie MeSH
- lektiny typu C metabolismus MeSH
- lidé MeSH
- modely nemocí na zvířatech MeSH
- myokard imunologie patologie metabolismus MeSH
- myokarditida * imunologie patologie metabolismus MeSH
- myosiny metabolismus MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- paměťové T-buňky * imunologie metabolismus MeSH
- srdeční myosiny imunologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- antigeny CD279 MeSH
- CD antigeny MeSH
- CD69 antigen MeSH Prohlížeč
- diferenciační antigeny T-lymfocytů MeSH
- inhibitory kontrolních bodů * MeSH
- lektiny typu C MeSH
- myosiny MeSH
- Pdcd1 protein, mouse MeSH Prohlížeč
- srdeční myosiny MeSH
Renal nerves play a critical role in cardiorenal interactions. Renal denervation (RDN) improved survival in some experimental heart failure (HF) models. It is not known whether these favorable effects are indirect, explainable by a decrease in vascular afterload, or diminished neurohumoral response in the kidneys, or whether RDN procedure per se has direct myocardial effects in the failing heart. To elucidate mechanisms how RDN affects failing heart, we studied load-independent indexes of ventricular function, gene markers of myocardial remodeling, and cardiac sympathetic signaling in HF, induced by chronic volume overload (aorto-caval fistula, ACF) of Ren2 transgenic rats. Volume overload by ACF led to left ventricular (LV) hypertrophy and dysfunction, myocardial remodeling (upregulated Nppa, MYH 7/6 genes), increased renal and circulating norepinephrine (NE), reduced myocardial NE content, increased monoaminoxidase A (MAO-A), ROS production and decreased tyrosine hydroxylase (+) nerve staining. RDN in HF animals decreased congestion in the lungs and the liver, improved load-independent cardiac function (Ees, PRSW, Ees/Ea ratio), without affecting arterial elastance or LV pressure, reduced adverse myocardial remodeling (Myh 7/6, collagen I/III ratio), decreased myocardial MAO-A and inhibited renal neprilysin activity. RDN increased myocardial expression of acetylcholinesterase (Ache) and muscarinic receptors (Chrm2), decreased circulating and renal NE, but increased myocardial NE content, restoring so autonomic control of the heart. These changes likely explain improvements in survival after RDN in this model. The results suggest that RDN has remote, load-independent and favorable intrinsic myocardial effects in the failing heart. RDN therefore could be a useful therapeutic strategy in HF.
- Klíčová slova
- Heart failure, Norepinephrine, Renal denervation, Sympathetic nervous system, Volume overload,
- MeSH
- krysa rodu Rattus MeSH
- ledviny * inervace metabolismus MeSH
- modely nemocí na zvířatech * MeSH
- myokard * metabolismus MeSH
- noradrenalin * krev metabolismus MeSH
- potkani transgenní * MeSH
- remodelace komor fyziologie MeSH
- srdce inervace patofyziologie MeSH
- srdeční selhání * patofyziologie metabolismus MeSH
- sympatektomie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- noradrenalin * MeSH
BACKGROUND: Plasma donor-derived cell-free DNA (dd-cfDNA) is used to screen for rejection in heart transplants. We launched the Trifecta-Heart study ( ClinicalTrials.gov No. NCT04707872), an investigator-initiated, prospective trial, to examine the correlations between genome-wide molecular changes in endomyocardial biopsies (EMBs) and plasma dd-cfDNA. The present report analyzes the correlation of plasma dd-cfDNA with gene expression in EMBs from 4 vanguard centers and compared these correlations with those in 604 kidney transplant biopsies in the Trifecta-Kidney study ( ClinicalTrials.gov No. NCT04239703). METHODS: We analyzed 137 consecutive dd-cfDNA-EMB pairs from 70 patients. Plasma %dd-cfDNA was measured by the Prospera test (Natera Inc), and gene expression in EMBs was assessed by Molecular Microscope Diagnostic System using machine-learning algorithms to interpret rejection and injury states. RESULTS: Top transcripts correlating with dd-cfDNA were related to genes increased in rejection such as interferon gamma-inducible genes (eg, HLA-DMA ) but also with genes induced by injury and expressed in macrophages (eg, SERPINA1 and HMOX1 ). In gene enrichment analysis, the top dd-cfDNA-correlated genes reflected inflammation and rejection pathways. Dd-cfDNA correlations with rejection genes in EMB were similar to those seen in kidney transplant biopsies, with somewhat stronger correlations for TCMR genes in hearts and ABMR genes in kidneys. However, the correlations with parenchymal injury-induced genes and macrophage genes were much stronger in hearts. CONCLUSIONS: In this first analysis of Trifecta-Heart study, dd-cfDNA correlates significantly with molecular rejection but also with injury and macrophage infiltration, reflecting the proinflammatory properties of injured cardiomyocytes. The relationship supports the utility of dd-cfDNA in clinical management of heart transplant recipients.
- MeSH
- biologické markery krev MeSH
- biopsie MeSH
- dárci tkání * MeSH
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- myokard * patologie metabolismus MeSH
- prediktivní hodnota testů MeSH
- prospektivní studie MeSH
- rejekce štěpu * genetika imunologie patologie krev diagnóza MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- transplantace ledvin škodlivé účinky MeSH
- transplantace srdce * škodlivé účinky MeSH
- volné cirkulující nukleové kyseliny * krev genetika MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- pozorovací studie MeSH
- srovnávací studie MeSH
- Názvy látek
- biologické markery MeSH
- volné cirkulující nukleové kyseliny * MeSH
The effects of alpha-pinene (AP), a monoterpenoid, known for its antioxidant, anti-inflammatory, and anti-apoptotic properties, on methotrexate (MTX)-induced cardiac and hepatic damage were investigated in this study. Male Sprague-Dawley rats were divided into Control, Vehicle, AP, MTX, and AP+MTX groups (n=7). AP (50 mg/kg/day, 14 days) was applied subcutaneously in the AP and AP+MTX groups. MTX (20 mg/kg) was injected three days before sacrification. Serum CK-MB, troponin T, ALT, and AST levels, as well as cardiac and hepatic MDA, GSH, caspase-3, and p53 levels, were measured by ELISA. Histological changes in tissues were evaluated by scoring in terms of tissue damage and cellular degeneration parameters after hematoxylin-eosin staining. MTX caused significant increase in serum CK-MB, troponin T, ALT, and AST levels, hepatic and cardiac lipid peroxidation, GSH depletion, and caspase-3 level. However, tissue levels of p53 did not change significantly. MTX-induced histological deterioration was observed in both tissues. These MTX-induced changes were significantly reduced in the AP+MTX group. Present results show that MTX-induced cardiac and hepatic damage is prevented by AP pretreatment. This protection can be attributed to the antioxidant and anti-apoptotic properties of AP. Considering the importance of MTX in cancer treatment, AP appears to have highly promising potential as a cardioprotective and hepatoprotective agent in anti-tumoral therapy. Key words: MDA, GSH, Caspase-3, p53, Oxidative stress, Apoptosis.
- MeSH
- antioxidancia farmakologie MeSH
- bicyklické monoterpeny * farmakologie MeSH
- játra účinky léků patologie metabolismus MeSH
- krysa rodu Rattus MeSH
- lékové postižení jater prevence a kontrola patologie metabolismus MeSH
- methotrexát * toxicita MeSH
- monoterpeny farmakologie terapeutické užití MeSH
- myokard patologie metabolismus MeSH
- oxidační stres účinky léků MeSH
- potkani Sprague-Dawley * MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- alpha-pinene MeSH Prohlížeč
- antioxidancia MeSH
- bicyklické monoterpeny * MeSH
- methotrexát * MeSH
- monoterpeny MeSH
Hyperhomocysteinemia (HHcy) is considered an independent risk factor of cardiovascular diseases. Among the proposed mechanisms underlying homocysteine toxicity are altered protein expression and induction of oxidative stress. In the present study, we explored protein abundance and parameters related to oxidative stress in heart homogenates of rats exposed to chronic mild HHcy. Using two-dimensional gel electrophoresis followed by MALDI-TOF/TOF mass spectrometry 22 altered proteins (6 upregulated and 14 downregulated) were identified. For eight proteins the altered abundances were validated by Western blot analysis. Identified proteins are primarily involved in energy metabolism (mainly enzymes of glycolysis, pyruvate dehydrogenase complex, citric acid cycle, and ATP synthase), cardiac muscle contraction (alpha-actin and myosin light chains), stress response (heat-shock protein beta1 and alphaB-crystallin) and antioxidant defense (glutathione peroxidase 1). Diminished antioxidant defense was confirmed by decreases in total antioxidant capacity and GSH/GSSG ratio. Consistent with the decline in enzymatic and non-enzymatic antioxidant defense the protein oxidative modification, as determined by tyrosine nitration, was significantly increased. These findings suggest that both, altered protein expression and elevated oxidative stress contribute to cardiovascular injury caused by HHcy. Keywords: Homocysteine, Heart, Protein abundance, Antioxidant capacity, Nitrotyrosines.
