Search Results for: Sclerosi multipla e legame con il virus della mononucleosi

Oncologi, ‘subito un piano di recupero per la prevenzione’

Annals of Internal Medicine, Ahead of Print.

Annals of Internal Medicine, Ahead of Print.

Introduction
Janus kinase (JAK) inhibitors are an important therapeutic option in the treatment of rheumatoid arthritis, but increase the risk of developing herpes zoster. Although a dry recombinant zoster vaccine (RZV) that can be used under immunosuppressive conditions has recently been developed, its optimal use and appropriate timing in patients scheduled to start JAK inhibitors is still unclear. The present study is designed to clarify the appropriate timing of JAK inhibitor initiation to measure varicella zoster virus (VZV)-specific IgG titers and VZV-specific T cell response in patients with rheumatoid arthritis who start tofacitinib at the first RZV vaccination or at the second one.

Methods and analysis
STOP HZ (Effectiveness and S afe T y O f P rophylactic Recombinant H erpes Z oster Virus Vaccination for Rheumatoid Arthritis Patients with Tofacitinib Treatment) study is a multicentre, open-label, randomised, comparative study in patients with rheumatoid arthritis who are scheduled to start tofacitinib. This study enrols 60 study subjects in 12 sites. Enrolled subjects receive RZV two times on day 1 and week 8 and initiate tofacitinib 5 mg two times a day at the time of their first RZV (day 1, group A) or second RZV (week 8, group B) based on randomisation. The random assignment is performed centrally in a 1:1 ratio. Patients in Group B continue the same treatment until the start of tofacitinib treatment. Primary endpoint is VZV-specific IgG antibody titers at week 12 compared with those at baseline in each group. Secondary endpoints include comparison of VZV-specific IgG antibody between the groups, changes in disease activity of rheumatoid arthritis, VZV-specific T cell response and adverse events.

Ethics and dissemination
The study has been approved by the Certified Review Board of Keio (No. 2022008), and conforms to the Declaration of Helsinki and good clinical practice guidelines. Written informed consent is obtained from participants prior to enrolment. The results of this study are planned to be submitted for publishment in relevant peer-review journals.

Trial registration number
jRCTs031230329.

The US Centers for Disease Control and Prevention (CDC) issued an updated advisory outlining prevention strategies for people visiting countries with widespread clade I mpox virus outbreaks. These strategies include getting the modified vaccinia Ankara–Bavarian Nordic (JYNNEOS) vaccine, which the World Health Organization recently prequalified.

Chronic hepatitis B virus (HBV) infection remains a significant global health burden, affecting over 250 million people worldwide who are at risk of developing liver cirrhosis and hepatocellular carcinoma (HCC). Currently available nucleos(t)ide analogues (NAs) are effective in controlling viraemia; however, functional cure, defined as loss of hepatitis B surface antigen (HBsAg), is rare and difficult to achieve and likely requires robust immune responses, reflecting the need for innovative therapeutic strategies.1 Thus, the future of treating chronic HBV infections relies on combination therapies that include both direct-acting antiviral agents and immunomodulatory agents.2 In this context, selgantolimod (SLGN), an agonist of Toll-like receptor 8 (TLR8), could be a promising candidate. Its efficacy in the treatment of chronic HBV infections has been investigated in preclinical models and clinical trials,3–5 but there remains limited understanding of its impact on immune effectors within the…

Circulation, Volume 150, Issue Suppl_1, Page A4123674-A4123674, November 12, 2024. Background:Transplantation arteriosclerosis is one of the major complications for the mid- and long-term survival of recipients with organ transplantation. Although previous studies suggest that CD34 stem/progenitor cells are involved in this process, the heterogeneity and potential adverse effects of CD34+SPCs have not been fully determined.Methods and Results:A mouse model of transplant arteriosclerosis was established by using Balb/c, C57BL/6J, CD34-CreERT2, R26-tdTomato, Rosa26-iDTR, CD34-Dre, PI16-CreERT2, CAG-LSL-RSR-tdTomato-2A-DTR mice. Using single-cell RNA-seq and the innovative application of genetic lineage tracing with dual recombinases, we identified a subpopulation of fibroblast progenitor cells marked by high CD34 and PI16 expression. Interestingly, this progenitor cell group gave rise to a distinct chemotactic fibroblast subset. Based on chemokine antibody microarray assay and transcriptome analysis, the subgroup with increased CD34 expression and decreased PI16 expression promoted intimal hyperplasia, acting through the paracrine release of a specific chemokine CCL11 (eotaxin-1). Moreover, the binding of CCL11 to its receptor CCR3 triggered the PI3K-AKT signaling pathway in smooth muscle cells, promoting their proliferation and migration to form neointimal lesions. Overexpression of CCL11 by adeno-associated virus can promote neointimal hyperplasia in vivo, while neutralization of CCL11 or inhibition of receptor CCR3 can alleviate neointimal lesions.Conclusion:Our findings identified CD34+/PI16+fibroblast progenitors able to differentiate into specific chemotactic fibroblasts that release chemokines pivotal for neointima formation, implicating a therapeutic potential targeting the chemotactic behavior of these cells.

Circulation, Volume 150, Issue Suppl_1, Page A4144514-A4144514, November 12, 2024. Introduction:Human Immunodeficiency Virus Associated Cardiomyopathy (HIVAC) is characterized by left ventricular (LV) systolic or diastolic dysfunction with or without LV dilatation and heart failure symptoms. The introduction of antiretroviral therapy (ART) has changed the fulminant systolic heart failure presentation of HIV myocarditis to diastolic heart failure. We present a unique case of dilated cardiomyopathy in a young patient without advanced HIV illness which has rarely been documented in the literature. This is a rare presentation of HIVAC in the post-ART era.Case Report:A 32-year-old male with a past medical history (PMH) of the human immunodeficiency virus (HIV) presented with complaints of new onset worsening shortness of breath and lower extremity edema for four weeks. He was diagnosed with HIV seven years ago and was not compliant with ART. Laboratory testing showed a cluster of differentiation 4 (CD4) 823 and HIV load 2550. Myocarditis was ruled out by normal troponin levels and no new changes on the electrocardiogram (ECG). Transthoracic echocardiogram (TTE) showed dilated left ventricle (LV), LV global hypokinesis, LV ejection fraction (LVEF) 10-15%, dilated right ventricle, biatrial dilation, moderate to severe mitral regurgitation, severe tricuspid regurgitation, pulmonary artery (PA) systolic pressure 73 mmHg and no pericardial effusion. Coronary angiography was negative for coronary artery disease (CAD). The patient was started on carvedilol and outpatient evaluation for a left ventricular assistance device.Discussion:Systolic dysfunction in patients with HIVAC carried a poor prognosis in the pre-ART era and was common in patients with elevated c-reactive protein (CRP), tobacco use, and previous myocardial infarction (MI). After the advent of ART, systolic dysfunction is rare and replaced by diastolic cardiomyopathy in the setting of ART use. Diagnosis is usually by excluding other etiologies and biopsy is not necessarily required. Management is usually guideline-directed medical therapy (i.e. beta blocker, renin-angiotensin-aldosterone antagonists, sodium-glucose cotransporter-2) and device-based therapy but there is still data lacking to assess its benefit.

Circulation, Volume 150, Issue Suppl_1, Page A4139176-A4139176, November 12, 2024. Introduction:During natural aging, physiological remodeling of the heart is a critical for the cardiovascular disease and heart failure. miR-30a-5p is related to kidney injury, cancer, and autoimmune diseases. However, whether miR-30a-5p has an effect in cardiac aging has yet to be explored.Hypothesis:This study aimed to characterize the role and mechanism of action of miR-30a-5p in cardiac senescence.Methods:We established miR-30a-5p knockout/overexpressing mouse model. Natural heart aging (18-months-old) and D-galactose-induced aging mouse model were established. The mechanism was explored in D-galactose- or 10-days-cultured cardiomyocytes.Results:miR-30a-5p was downregulated in aged mouse hearts and neonatal rat cardiomyocytes (NRCMs). In vivo, using a combination of echocardiography and different molecular biological approaches, we investigated the role of miR-30a-5p knockout or overexpressed mice on natural- or D-galactose-induced heart aging. In vitro, using RNA-sequence and a series of molecular biology, the mechanism of miR-30a-5p-regulated cardiac senescence was explored in cardiomyocytes. miR-30a-5p knockout mice showed aggravated natural- or D-galactose-induced heart aging compared to wild-type littermate mice, with significantly decreased heart function, increased number of γH2AX-positive cells, reduced telomere length, and upregulated p21 and p53 expression. Cardiac-specific knockdown of miR-30a-5p using adeno-associated virus 9 in D-galactose-induced senescent wild-type mice showed effects similar to those observed in knockout mice. Notably, overexpression of miR-30a-5p in wild-type murine hearts alleviated D-galactose-induced heart senescence by improving heart function, increasing telomere length, decreasing the number of γH2AX-positive cells, and downregulating p53 and p21 expression. This was confirmed in D-galactose-treated or naturally aged NRCMs. Mechanistically, TP53INP1 was identified as a target of miR-30a-5p by mediating the SUMOylation of TP53INP1 and its translocation from the cytoplasm to the nucleus to interact with p53. Further evidence demonstrated that cardiac-specific TP53INP1 deficiency ameliorates miR-30a-5p knockout-aggravated cardiac dysfunction and heart senescence.Conclusions:This study identified miR-30a-5p as a crucial modulator of heart senescence and revealed that the miR-30a-5p–TP53INP1–p53 axis is essential for heart and cardiomyocyte aging.

Circulation, Volume 150, Issue Suppl_1, Page A4122301-A4122301, November 12, 2024. Background:Recent studies in both human genetics and mouse models have highlighted the significance of phosphatidylinositol (PI) in the progression of fatty liver disease (FLD). Despite this, the precise mechanisms underlying PI’s role remain elusive.Aims:This study aimed to elucidate the involvement of PI in FLD by disrupting hepatic PI biosynthesis through modulation of CDP-diacylglycerol synthase 2 (CDS2) expression, the primary enzyme in PI biosynthesis (A).Methods:We generated liver-specific knockouts of CDS2 and SCAP (SREBP cleavage-activating protein) using adeno-associated virus (AAV) expressing sgRNA against each gene. Phospholipid species were analyzed and quantified by LC/MS.Results:CDS2 liver-specific knockout mice (B, C) exhibited a pronounced development of fatty liver, characterized by elevated triglyceride and cholesterol levels (C). Notably, liver PI levels were significantly reduced in CDS2 knockout mice (E), accompanied by dysregulated activation of sterol regulatory element-binding protein (SREBP) even during fasting conditions (F), leading to increased de novo lipogenesis. Intraperitoneal administration of exogenous PI effectively normalized SREBP cleavage (G), highlighting PI’s critical role in SREBP regulation. Furthermore, simultaneous knockout of SCAP with CDS2 restored the normal liver phenotype, implicating SREBP activation as a central mechanism underlying fatty liver development in CDS2 knockout mice (H, I).Conclusion:Deletion of CDS2 in the liver reduced PI levels, subsequently inducing significant fatty liver due to dysregulated SREBP activation. This study underscores the importance of CDS2 in maintaining PI homeostasis, which in turn regulates SREBP activity and lipid metabolism. Our findings provide valuable insights into the pathogenesis of metabolic disorders and offer potential therapeutic strategies for targeting FLD.

Circulation, Volume 150, Issue Suppl_1, Page A4144743-A4144743, November 12, 2024. Case description: >A 38-year-old male with a history of paroxysmal atrial fibrillation status post-RFA ablation, presented to the emergency department (ED) with a 3-week history of non-bloody diarrhea, abdominal cramping, nausea, fever, and headache after a trip to Guatemala. In the ED, his vital signs were temperature (99.3 °F), and heart rate (116 bpm). Notable physical exam findings were diffuse erythematous macular rash and conjunctival injection. Initial labs demonstrated elevated white count (15,100 K/mcL) and lactate (3.2 mmol/L). He was treated with ceftriaxone and metronidazole, with clinical improvement. Stool cultures were positive for salmonella and cyclospora cayetanensis. On hospital day 3, he developed severe substernal chest pain, minimal ST elevation in the anterolateral leads on ECG and elevated HS- troponin levels of 7000 ng/ml, peak of 12000 ng/ml. Transthoracic echocardiogram showed normal LV systolic function, with no evidence of pericardial effusion and regional wall motion abnormalities. Subsequent cardiac MRI demonstrated evidence of myopericarditis(anterior and lateral pericardial enhancement, along with focal epicardial late gadolinium enhancement in the mid inferolateral wall of the left ventricle with associated myocardial edema, and a small pericardial effusion). He was discharged home on Trimethoprim-Sulfamethoxazole and started on colchicine, with no recurrent chest pain.Discussion:Myopericarditis is a complication of acute pericarditis due to pericardial inflammation extension to the myocardium. It is usually caused by a virus and rarely due to bacteria as demonstrated by this case, presenting as elevated troponin levels and ST-segment elevation on ECG. To our knowledge, there are no known reports of cyclospora cayetanensis causing myopericarditis. The adherence of the salmonella bacteria to the cardiac endothelium can result in myocyte necrosis and release of self-antigens leading to the development of antibodies and autoimmune myocarditis. Long-term management of bacterial myopericarditis is dependent on the severity of the clinical presentation and includes antibiotics, anti-inflammatory medications, and colchicine. Most patients recover within one month, but persistent cardiac dysfunction and progression to end-stage dilated cardiomyopathy can occur, thus follow-up echocardiography is recommended.

Circulation, Volume 150, Issue Suppl_1, Page A4120830-A4120830, November 12, 2024. Case Presentation:Clozapine is an antipsychotic used in treatment-resistant schizophrenia. Its use has been limited by adverse events, rarely including myocarditis. Here, we describe a rare case of clozapine-induced myocarditis and the improvement of cardiac function with avoidance of clozapine for one week and initiation of guideline-directed medical therapy (GDMT).A 29-year-old man with schizophrenia on risperidone and paroxetine was admitted with schizophrenia decompensation and suicidal ideations. He was transitioned to clozapine with improvement in his psychiatric symptoms. Thirteen days after starting clozapine, he developed nausea, vomiting, tachycardia, and low-grade fever. He had leukocytosis but it was thought to be, in part, secondary to methylprednisolone before rituximab infusions for his multiple sclerosis. An electrocardiogram revealed sinus tachycardia, and troponin, which was taken in the setting of clozapine therapy, was 6.Four days later, his fever and tachycardia with chills and dyspnea persisted; troponin was in the forties and increased to 235 within a few hours. Over the next 36 hours, troponin peaked at 3,600. C-reactive protein and erythrocyte sedimentation rates were elevated at 20.5 and 51, compared to 1.8 and 3 respectively upon initiation of symptoms a few days earlier. A respiratory viral panel, blood and urine cultures, human immunodeficiency virus, and an autoimmune workup were unrevealing. Clozapine was held. A transthoracic echocardiogram revealed a reduced systolic function with a left ventricular ejection fraction (LVEF) of 40%. A cardiac magnetic resonance imaging revealed acute myocarditis with LVEF 24%. He was started on GDMT and a repeat echocardiogram six days later revealed normalization of systolic function with LVEF 56% with clinical improvement. His last dose of clozapine was seven days earlier. He was discharged on GDMT and clozapine was added to his allergy list.Discussion:Myocarditis is a serious and rare adverse event to clozapine therapy. Symptoms are non-specific and delays in diagnosis may lead to myocardial damage and fatal arrhythmias. In light of the patient’s presentation, unrevealing workup, and improvement with avoidance of clozapine, we believe that the individual had clozapine-induced myocarditis. It is important to highlight the occurrence of this rare outcome to consider this toxicity and initiate treatment in time.

Circulation, Volume 150, Issue Suppl_1, Page A4123849-A4123849, November 12, 2024. Background:Older adults and adults with comorbidities are at increased risk for severe respiratory syncytial virus (RSV) disease and related complications.Aims:To estimate the risk of myocardial infarction (MI) and all−cause mortality among adults aged ≥50 years hospitalized with RSV compared to those with no recent acute respiratory illness (ARI) and those hospitalized with influenza.Methods:Data from Optum’s de−identified Clinformatics® Data Mart Database were analyzed (October 2015–June 2023) in this retrospective cohort study. Adults aged ≥50 years with ≥12 months of continuous enrollment were assigned to cohorts based on RSV or influenza hospitalization (from ICD−10 codes; RSV and flu cohorts) or no recent ARI (control cohort). Index dates for RSV and flu cohorts were the start of an ARI that included hospitalization. Baseline characteristics were measured in the 12 months pre−index. MI (from ICD−10 codes) and all−cause mortality were measured during follow−up and compared between cohorts using time−varying coefficient multivariable adjusted Cox models (MI results accounted for the competing risk of death).Results:In the RSV cohort (n=14,759), mean age (76.5 years) and mean Charlson comorbidity index (CCI; 3.3) were higher than the flu (n=77,468; 75.4 years, CCI=2.9) and control (n=73,795; 69.5 years, CCI=1.0) cohorts. Adjusted HRs (95% CI) for MI and all−cause mortality risk were significantly higher in the RSV vs control cohort across follow−up, ranging from 30.96 (26.22–36.54) within 30 days post−index to 2.26 (2.04–2.51) >365 days post−index for MI and 10.77 (9.19–12.63) within 30 days post−index to 2.29 (2.18–2.42) >365 days post−index for mortality. Compared to the flu cohort, adjusted MI and mortality risk in the RSV cohort were lower during the 30 days post−index (MI: 0.87 [0.82–0.92]; mortality: 0.84 [0.78–0.90]) but higher >365 days post−index (MI: 1.11 [1.01–1.22]; mortality: 1.05 [1.01–1.10]).Conclusion:MI and all−cause mortality risk were higher for hospitalized RSV cases compared to controls. Smaller differences in outcomes were observed when comparing hospitalized RSV cases with hospitalized influenza cases, with varying direction over time. With existing evidence of increased MI and mortality risk after influenza and these findings on MI and mortality risk after RSV, future research should aim to further understand the impact of RSV on cardiovascular outcomes and assess the role of RSV prevention in lowering the risk of MI and mortality.

Circulation, Volume 150, Issue Suppl_1, Page A4143634-A4143634, November 12, 2024. Background:Cardiac microvascular dysfunction is a contributing factor to cardiac ischemia/reperfusion (I/R) injury. The impact of mammalian Ste20-like kinase 4 (MST4) on cardiac microvascular I/R injury remains unknown.Aims:To decipher the role of MST4 in cardiac microvascular I/R injury and the underlying mechanisms.Methods:Single-cell RNA sequencing was performed to explore the expression changes of MST4 in different cardiac cell types. Myeloid-specific MST4 knockout mice (MST4 CKO) and bone marrow transplantation were used to testify to the role of myeloid-derived MST4 in cardiac microvascular I/R injury. Bone-marrow-derived macrophage (BMDM) and cardiac microvascular endothelial cells (CMEC) were used to dissect molecular mechanisms. Adeno-associated virus and adenovirus were constructed to overexpress ATP Citrate Lyase (ACLY) with mutation of serine 455 (S455A) in vivo and in vitro, respectively.Results:MST4 was dominantly upregulated in CCR2+ monocyte-derived macrophages. Myeloid-specific deficiency of MST4 or wild type mice that were transplanted with BMDM from MST4 CKO mice improves cardiac performance in the I/R mouse model. Metabolomics showed that the primary bile acid biosynthesis pathway was upregulated in BMDM overexpressing MST4. The level of 7α-hydroxyl3-oxo-4-cholestenoic acid (7-HOCA), an intermediate of bile acid, was dramatically increased in I/R mice or BMDM overexpressing MST4, which can be reversed by knocking down MST4. Phosphoproteomics and LC-MS/MS analysis discovered that ACLY was one of the most important substrates of MST4 in the process of I/R injury. ACLY was directly phosphorylated by MST4 at serine 455, which increased ACLY enzyme activity. Mechanistically, ACLY promoted cholesterol catabolism through the bile acid synthesis pathway, leading to the accumulation of 7-HOCA in the macrophage-endothelial cell microenvironment. A high level of 7-HOCA was able to promote endothelial cell mtDNA release, leading to endothelial cell pyroptosis through the inflammasome pathway. However, mutation of serine 455 of ACLY blocked the role of MST4.Conclusions:Our data defined a previously unrecognized role of the MST4/ACLY pathway in cardiac microvascular I/R injury. MST4 led to the accumulation of 7-HOCA by phosphorylating ACLY, furthermore, 7-HOCA promoted endothelial cell injury. Targeting the MST4/ACLY pathway ameliorated cardiac microvascular I/R injury, which may provide a novel therapeutic strategy for I/R injury.

Circulation, Volume 150, Issue Suppl_1, Page A4137845-A4137845, November 12, 2024. Introduction:Pulmonary arterial hypertension (PAH) is a disaster disease characterized by obliterative vascular remodeling and persistent increase of vascular resistance, leading to right heart failure and premature death. Understanding the cellular and molecular mechanisms will help develop novel therapeutic approaches for PAH patients.Hypothesis:We hypothesis that single-cell RNA sequencing analysis can help understand the cellular and molecular mechanisms that drive the disease initiation and progression.Methods:10 healthy donors, 10 idiopathic PAH, 10 drug and toxin induced PAH, 10 systemic and pulmonary shunting induced PAH patients from both male and female, and different ethical groups and races, and ages were obtained from PHBI. Lung tissue specimens were processed for fixed scRNA-seq. The cell proportion change, gene expression, and pathway analysis were evaluated between different disease subclasses, sex, age on different cell types.Results:Our analysis reveals 317,414 cells, 33 clusters and 9 major cell types, including endothelial cells (ECs), alveolar cells, fibroblast, smooth muscle cells (SMCs), pericytes, myeloid cells, lymphocytes, airway epithelial cells, platelet. Cell proportion analysis demonstrated an increase in the proportions of venous ECs, adventitial fibroblasts and myofibroblasts, alveolar macrophages, B cells, plasma cells and a reduction in capillary ECs 2 and pericytes in PAH lungs. KEGG Pathway analysis showed that upregulated pathways related Herpes simplex virus 1 infection, ECM-receptor interaction, Complement and coagulation cascades, Hedgehog signaling, TGF-beta signaling pathway, and downregulated pathways related to IL-17 signaling, TNF signaling, MAPK signaling pathway were enriched in the PAH patients. Female PAH patients exhibit an increase of myofibroblasts and platelets proportion compared to male PAH patients. MsigDB Hallmark Pathway analysis showed that p53 pathway was upregulated, whereas Inflammatory Response, Hypoxia, Epithelial Mesenchymal Transition were downregulated in female PAH patients. PAH patients older than 21 years exhibit an increase in the cell proportion of Platelet, SMCs, Arterial ECs and Venous ECs, and alveolar macrophages and a reduction of B cells and plasma cells.Conclusions:Our integrated analysis of human PAH lung atlas dataset provides a comprehensive understanding of lung cell populations and molecular signature in PAH patients with different sex, age and subclasses

Circulation, Volume 150, Issue Suppl_1, Page A4134426-A4134426, November 12, 2024. Introduction:Viral myocarditis is an inflammatory disease of the myocardium that significantly contributes to sudden death in children and young adults. The COVID-19 pandemic underscores the critical need to understand the pathogenesis and develop effective treatment strategies for viral myocarditis.Methods:To investigate the role of the novel E3 ligase TRIM29 in viral myocarditis, we used wild-type and TRIM29 knockout mice infected with coxsackievirus B3 (CVB3) and encephalomyocarditis virus (EMCV), to induce the myocarditis. Additionally, wild-type mice infected with CVB3 were treated with the protein kinase RNA-like endoplasmic reticulum kinase (PERK) inhibitor GSK2656157 or a DMSO control to evaluate potential therapeutic interventions. Mice survival and heart function were monitored using transthoracic echocardiography, and hearts were harvested for histological and immunohistochemical analysis. Techniques including real-time PCR, western blotting, co-immunoprecipitation, enzyme-linked immunoassay, flow cytometry, over-expression, and knockdown were employed to elucidate the pathogenic mechanisms by which TRIM29 regulates the endoplasmic reticulum stress response after viral infection.Results:We found that TRIM29 was highly induced by cardiotropic viruses, including CVB3 and EMCV, and promoted PERK-mediated endoplasmic reticulum (ER) stress, apoptosis, and reactive oxygen species (ROS) responses, which restricted viral replication in cardiomyocytesin vitro. TRIM29 deficiency protected mice from viral myocarditis by enhancing cardiac antiviral functions and reducing PERK-mediated inflammation and immunosuppressive cellsin vivo. Mechanistically, TRIM29 interacted with PERK to catalyze the SUMOylation of PERK, maintaining its stability and thereby promoting PERK-mediated signaling pathways. Furthermore, we demonstrated that the PERK inhibitor GSK2656157 mitigated viral myocarditis by disrupting the TRIM29-PERK interaction, which improved cardiac function, enhanced cardiac antiviral responses, and reduced inflammation and immunosuppressive cellsin vivo.Conclusions:Our findings provide the first evidence that the TRIM29-PERK signaling axis can be targeted for the treatment of viral myocarditis. This suggests that targeting the TRIM29-PERK axis could effectively mitigate viral myocarditis and associated cardiovascular diseases.