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Circulation Research Jun 2024Fibroblasts are essential for building and maintaining the structural integrity of all organs. Moreover, fibroblasts can acquire an inflammatory phenotype to accommodate... (Review)
Review
Fibroblasts are essential for building and maintaining the structural integrity of all organs. Moreover, fibroblasts can acquire an inflammatory phenotype to accommodate immune cells in specific niches and to provide migration, differentiation, and growth factors. In the heart, balancing of fibroblast activity is critical for cardiac homeostasis and optimal organ function during inflammation. Fibroblasts sustain cardiac homeostasis by generating local niche environments that support housekeeping functions and by actively engaging in intercellular cross talk. During inflammatory perturbations, cardiac fibroblasts rapidly switch to an inflammatory state and actively communicate with infiltrating immune cells to orchestrate immune cell migration and activity. Here, we summarize the current knowledge on the molecular landscape of cardiac fibroblasts, focusing on their dual role in promoting tissue homeostasis and modulating immune cell-cardiomyocyte interaction. In addition, we discuss potential future avenues for manipulating cardiac fibroblast activity during myocardial inflammation.
Topics: Humans; Homeostasis; Animals; Fibroblasts; Myocardium; Inflammation; Myocarditis; Myocytes, Cardiac; Cell Communication
PubMed: 38843287
DOI: 10.1161/CIRCRESAHA.124.323892 -
Circulation Research Jun 2024Over the past 30 years, the field of cardioimmunology has moved from being dismissed as a field that was chasing an epiphenomenon of little biological consequence to a... (Review)
Review
Over the past 30 years, the field of cardioimmunology has moved from being dismissed as a field that was chasing an epiphenomenon of little biological consequence to a scientific discipline that is providing important new insights into the immunologic basis for hypertension, atherosclerosis, myocarditis, pericarditis, autoimmune heart disease, and heart failure. In this article, we will review the conceptual insights and technical breakthroughs that have allowed the field to move forward, as well as the clinical trials in the cardioimmunology space, to provide a historical context for the articles that will appear in the compendium that is focused on the interface between cardioimmunology, myocardial function, and disease.
Topics: Humans; Animals; Heart Diseases; Allergy and Immunology; Cardiovascular Diseases; History, 21st Century; History, 20th Century
PubMed: 38843286
DOI: 10.1161/CIRCRESAHA.123.323656 -
Human Vaccines & Immunotherapeutics Dec 2024Recombinant protein vaccines represent a well-established, reliable and safe approach for pandemic vaccination. SpikoGen® is a recombinant spike protein trimer... (Review)
Review
Recombinant protein vaccines represent a well-established, reliable and safe approach for pandemic vaccination. SpikoGen® is a recombinant spike protein trimer manufactured in insect cells and formulated with Advax-CpG55.2 adjuvant. In murine, hamster, ferret and non-human primate studies, SpikoGen® consistently provided protection against a range of SARS-CoV-2 variants. A pivotal Phase 3 placebo-controlled efficacy trial involving 16,876 participants confirmed the ability of SpikoGen® to prevent infection and severe disease caused by the virulent Delta strain. SpikoGen® subsequently received a marketing authorization from the Iranian FDA in early October 2021 for prevention of COVID-19 in adults. Following a successful pediatric study, its approval was extended to children 5 years and older. Eight million doses of SpikoGen® have been delivered, and a next-generation booster version is currently in development. This highlights the benefits of adjuvanted protein-based approaches which should not overlook when vaccine platforms are being selected for future pandemics.
Topics: COVID-19 Vaccines; Animals; Spike Glycoprotein, Coronavirus; Humans; COVID-19; Vaccines, Synthetic; SARS-CoV-2; Adjuvants, Vaccine; Adjuvants, Immunologic; Vaccine Development
PubMed: 38839044
DOI: 10.1080/21645515.2024.2363016 -
Revista Brasileira de Parasitologia... 2024In endemic areas for canine visceral leishmaniasis (CVL), the occurrence of coinfection with other pathogens, such as Ehrlichia spp., has been associated with worsening...
In endemic areas for canine visceral leishmaniasis (CVL), the occurrence of coinfection with other pathogens, such as Ehrlichia spp., has been associated with worsening of the clinical condition. The study aimed to evaluate the occurrence of histological changes in the myocardia of dogs naturally infected with Leishmania chagasi with or without coinfection with Ehrlichia spp.. We evaluated paraffin-embedded myocardial sections from 31 dogs, affected by either L. chagasi alone or coinfected with L. chagasi and Ehrlichia spp., to compare the extent and degree of cardiac damage. The blocks were divided into two groups. G1 (dogs infected only by L. chagasi) and G2 (dogs coinfected with L. chagasi and Ehrlichia spp.). The right atrium free wall, right ventricle free wall, left ventricle, and interventricular septum of all groups were evaluated. Cardiac alterations were observed in 41.93% (52/124) of the fragments evaluated and inflammatory infiltrate was the most common pattern found. The G2 group showed a higher incidence of myocarditis, with 61.53% (32/52), compared to the G1 group, in which 20 out of 72 cases (27.7%) exhibited histopathological changes (p <0.05). These findings confirmed that coinfection can potentiate cardiac damage in dogs.
Topics: Animals; Dogs; Leishmaniasis, Visceral; Dog Diseases; Male; Ehrlichiosis; Coinfection; Female; Myocarditis; Ehrlichia; Myocardium
PubMed: 38836809
DOI: 10.1590/S1984-29612024023 -
Frontiers in Cardiovascular Medicine 2024Neonatal (enteroviral) myocarditis (NM/NEM) is rare but unpredictable and devastating, with high mortality and morbidity. We report a case of neonatal coxsackievirus B...
BACKGROUND
Neonatal (enteroviral) myocarditis (NM/NEM) is rare but unpredictable and devastating, with high mortality and morbidity. We report a case of neonatal coxsackievirus B (CVB) fulminant myocarditis successfully treated with veno-arterial extracorporeal membrane oxygenation (V-A ECMO).
CASE PRESENTATION
A previously healthy 7-day-old boy presented with fever for 4 days. Progressive cardiac dysfunction (weak heart sounds, hepatomegaly, pulmonary edema, ascites, and oliguria), decreased left ventricular ejection fraction (LVEF) and fractional shortening (FS), transient ventricular fibrillation, dramatically elevated creatine kinase-MB (405.8 U/L), cardiac troponin I (25.85 ng/ml), and N-terminal pro-brain natriuretic peptide (NT-proBNP > 35,000 ng/L), and positive blood CVB ribonucleic acid indicated neonatal CVB fulminating myocarditis. It was refractory to mechanical ventilation, fluid resuscitation, inotropes, corticosteroids, intravenous immunoglobulin, and diuretics during the first 4 days of hospitalization (DOH 1-4). The deterioration was suppressed by V-A ECMO in the next 5 days (DOH 5-9), despite the occurrence of bilateral grade III intraventricular hemorrhage on DOH 7. Within the first 4 days after ECMO decannulation (DOH 10-13), he continued to improve with withdrawal of mechanical ventilation, LVEF > 60%, and FS > 30%. In the subsequent 4 days (DOH 14-17), his LVEF and FS decreased to 52% and 25%, and further dropped to 37%-38% and 17% over the next 2 days (DOH 18-19), respectively. There was no other deterioration except for cardiomegaly and paroxysmal tachypnea. Through strengthening fluid restriction and diuresis, and improving cardiopulmonary function, he restabilized. Finally, notwithstanding NT-proBNP elevation (>35,000 ng/L), cardiomegaly, and low LVEF (40%-44%) and FS (18%-21%) levels, he was discharged on DOH 26 with oral medications discontinued within 3 weeks postdischarge. In nearly three years of follow-up, he was uneventful, with interventricular septum hyperechogenic foci and mild mitral/tricuspid regurgitation.
CONCLUSIONS
Dynamic cardiac function monitoring via real-time echocardiography is useful for the diagnosis and treatment of NM/NEM. As a lifesaving therapy, ECMO may improve the survival rate of patients with NM/NEM. However, the "honeymoon period" after ECMO may cause the illusion of recovery. Regardless of whether the survivors of NM/NEM have undergone ECMO, close long-term follow-up is paramount to the prompt identification and intervention of abnormalities.
PubMed: 38836060
DOI: 10.3389/fcvm.2024.1364289 -
ACG Case Reports Journal Jun 2024Cardiac extraintestinal manifestations (EIMs) of Crohn's disease (CD) are uncommon. They include pericarditis, myocarditis, and arrhythmias; however, distinguishing...
Cardiac extraintestinal manifestations (EIMs) of Crohn's disease (CD) are uncommon. They include pericarditis, myocarditis, and arrhythmias; however, distinguishing these from alternative causes including medication-related adverse effects is often challenging. Leukocytoclastic vasculitis is another uncommon EIM of CD that may present with systemic involvement. We present a rare case of myocarditis associated with leukocytoclastic vasculitis occurring as EIMs of CD. The myocarditis proved refractory to standard therapy and biologics targeting underlying gut inflammation. She developed an inflammatory cardiomyopathy and symptoms consistent with heart failure with preserved ejection fraction. Anakinra was tried, but despite the initial response, it should be used cautiously in patients with CD.
PubMed: 38835650
DOI: 10.14309/crj.0000000000001371 -
Scientific Reports Jun 2024Danshen, a prominent herb in traditional Chinese medicine (TCM), is known for its potential to enhance physiological functions such as blood circulation, immune...
Danshen, a prominent herb in traditional Chinese medicine (TCM), is known for its potential to enhance physiological functions such as blood circulation, immune response, and resolve blood stasis. Despite the effectiveness of COVID-19 vaccination efforts, some individuals still face severe complications post-infection, including pulmonary fibrosis, myocarditis arrhythmias and stroke. This study employs a network pharmacology and molecular docking approach to investigate the potential mechanisms underlying the therapeutic effects of candidate components and targets from Danshen in the treatment of complications in COVID-19. Candidate components and targets from Danshen were extracted from the TCMSP Database, while COVID-19-related targets were obtained from Genecards. Venn diagram analysis identified common targets. A Protein-Protein interaction (PPI) network and gene enrichment analysis elucidated potential therapeutic mechanisms. Molecular docking evaluated interactions between core targets and candidate components, followed by molecular dynamics simulations to assess stability. We identified 59 potential candidate components and 123 targets in Danshen for COVID-19 treatment. PPI analysis revealed 12 core targets, and gene enrichment analysis highlighted modulated pathways. Molecular docking showed favorable interactions, with molecular dynamics simulations indicating high stability of key complexes. Receiver operating characteristic (ROC) curves validated the docking protocol. Our study unveils candidate compounds, core targets, and molecular mechanisms of Danshen in COVID-19 treatment. These findings provide a scientific foundation for further research and potential development of therapeutic drugs.
Topics: Molecular Docking Simulation; Drugs, Chinese Herbal; Salvia miltiorrhiza; Humans; COVID-19 Drug Treatment; Network Pharmacology; Protein Interaction Maps; SARS-CoV-2; Molecular Dynamics Simulation; COVID-19; Medicine, Chinese Traditional
PubMed: 38834599
DOI: 10.1038/s41598-024-62363-x -
Clinical, Cosmetic and Investigational... 2024This case study outlines the management of a 24-year-old male with a history of juvenile nephronophthisis who underwent renal transplantation at age 12 and later...
This case study outlines the management of a 24-year-old male with a history of juvenile nephronophthisis who underwent renal transplantation at age 12 and later required dialysis at 18 due to chronic rejection and hypertension. Subsequently, the patient developed severe Hidradenitis Suppurativa (HS) affecting the axillary, groin, and gluteal regions. Despite undergoing various systemic and intravenous antibiotic therapies, as well as Adalimumab treatment, the HS remained refractory. Adalimumab was discontinued due to a detected ejection fraction of 45% during cardiologic follow-up, likely due to COVID-19 related myocarditis. Following this, the patient was initiated on secukinumab therapy, initially undergoing an induction phase followed by maintenance dosing. Significant improvements were observed in quality of life, pain scores, and HS activity after 5 weeks of secukinumab therapy, with sustained benefits at the 6-month follow-up. Secukinumab was well tolerated, with no reported adverse events. This case underscores the effectiveness and safety of secukinumab as a therapeutic option for refractory HS, particularly in patients with comorbidities such as renal transplant recipients.
PubMed: 38831783
DOI: 10.2147/CCID.S468268 -
Journal of Cardiology Cases Jun 2024Herein, we report a case of myocarditis in a 27-year-old male with long-term follow-up using longitudinal peak systolic strain (LPSS) measurements with transthoracic...
UNLABELLED
Herein, we report a case of myocarditis in a 27-year-old male with long-term follow-up using longitudinal peak systolic strain (LPSS) measurements with transthoracic echocardiography (TTE) and late gadolinium enhancement (LGE) in cardiovascular magnetic resonance imaging (CMR). On admission, a predominant decrease was observed in the LPSS in the posterolateral segments of the TTE. After a period of two weeks, the values of the LPSS observed in the posterolateral segments were still slightly reduced, which is consistent with the LGE results in CMR. After a duration of 16 months, an improvement was noted in the LPSS and LGE results in all the segments. Moreover, a time-phase discrepancy was observed in the segmental longitudinal strain curve for a period of two weeks from the onset of myocarditis. However, an improvement in the discrepancy was detected after 16 months.
LEARNING OBJECTIVE
Longitudinal peak systolic strain (LPSS) on transthoracic echocardiography (TTE) has predominantly focused on diagnosing the acute phase of myocarditis. Herein, LPSS was evaluated not only in the acute phase but also in the chronic phase. Furthermore, the relationship between the results of segmental LPSS and late gadolinium enhancement was documented. We would like to emphasize the usefulness of LPSS on TTE both for identifying myocarditis and as a tool for the long-term follow-up of patients.
PubMed: 38826761
DOI: 10.1016/j.jccase.2024.02.009 -
Scientific Reports Jun 2024Nonischaemic myocardial fibrosis is associated with cardiac dysfunction, malignant arrhythmias and sudden cardiac death. In the absence of a specific aetiology, its...
Nonischaemic myocardial fibrosis is associated with cardiac dysfunction, malignant arrhythmias and sudden cardiac death. In the absence of a specific aetiology, its finding as late gadolinium enhancement (LGE) on cardiac magnetic resonance imaging is often attributed to preceding viral myocarditis. Athletes presenting with ventricular arrhythmias often have nonischaemic LGE. Previous studies have demonstrated an adverse effect of exercise on the course of acute viral myocarditis. In this study, we have investigated, for the first time, the impact of endurance training on longer-term outcomes such as myocardial fibrosis and arrhythmogenicity in a murine coxsackievirus B3 (CVB)-induced myocarditis model. Male C57BL/6J mice (n = 72) were randomly assigned to 8 weeks of forced treadmill running (EEX) or no exercise (SED). Myocarditis was induced 2 weeks later by a single intraperitoneal injection with CVB, versus vehicle in the controls (PBS). In a separate study, mice (n = 30) were subjected to pretraining for 13 weeks (preEEX), without continuation of exercise during myocarditis. Overall, continuation of exercise resulted in a milder clinical course of viral disease, with less weight loss and better preserved running capacity. CVB-EEX and preEEX-CVB mice tended to have a lower mortality rate. At sacrifice (i.e. 6 weeks after inoculation), the majority of virus was cleared from the heart. Histological assessment demonstrated prominent myocardial inflammatory infiltration and cardiomyocyte loss in both CVB groups. Inflammatory lesions in the CVB-EEX group contained higher numbers of pro-inflammatory cells (iNOS-reactive macrophages and CD8 T lymphocytes) compared to these in CVB-SED. Treadmill running during myocarditis increased interstitial fibrosis [82.4% (CVB-EEX) vs. 56.3% (CVB-SED); P = 0.049]. Additionally, perivascular and/or interstitial fibrosis with extensive distribution was more likely to occur with exercise [64.7% and 64.7% (CVB-EEX) vs. 50% and 31.3% (CVB-SED); P = 0.048]. There was a numerical, but not significant, increase in the number of scars per cross-section (1.9 vs. 1.2; P = 0.195), with similar scar distribution and histological appearance in CVB-EEX and CVB-SED. In vivo electrophysiology studies did not induce sustained monomorphic ventricular tachycardia, only nonsustained (usually polymorphic) runs. Their cumulative beat count and duration paralleled the increased fibrosis between CVB-EEX and CVB-SED, but the difference was not significant (P = 0.084 for each). Interestingly, in mice that were subjected to pretraining only without continuation of exercise during myocarditis, no differences between pretrained and sedentary mice were observed at sacrifice (i.e. 6 weeks after inoculation and training cessation) with regard to myocardial inflammation, fibrosis, and ventricular arrhythmogenicity. In conclusion, endurance exercise during viral myocarditis modulates the inflammatory process with more pro-inflammatory cells and enhances perivascular and interstitial fibrosis development. The impact on ventricular arrhythmogenesis requires further exploration.
Topics: Animals; Myocarditis; Male; Mice; Physical Conditioning, Animal; Disease Models, Animal; Arrhythmias, Cardiac; Fibrosis; Enterovirus B, Human; Coxsackievirus Infections; Mice, Inbred C57BL; Myocardium; Endurance Training
PubMed: 38825590
DOI: 10.1038/s41598-024-61874-x