Blocking the IL-1β signalling pathway prevents chronic viral myocarditis and cardiac remodeling

Kraft, Lisa; Erdenesukh, Tugs; Sauter, Martina; Tschöpe, Carsten; Klingel, Karin

doi:10.1007/s00395-019-0719-0

Cited by 85 publications

(71 citation statements)

References 42 publications

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“…Findings from studies in animal models of viral and autoimmune myocarditis support a central role for NLRP3 inflammasome activation and subsequent IL-1β production in the pathogenesis of myocarditis 68,274 . Treatment with an anti-mouse IL-1β antibody at different stages of enteroviral infection prevented the development of chronic viral myocarditis by reducing inflammation, interstitial fibrosis and adverse cardiac remodelling in mice 274 . One clinical trial 275 and several case series 276,277 support the use of an anti-IL-1β monoclonal antibody for the treatment of recurrent pericarditis.…”

Section: Anti-il-1β and Anti-il-1 Receptor Antibodiesmentioning

confidence: 86%

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions

et al. 2020

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Inflammatory cardiomyopathy is defined as myocarditis in association with cardiac dysfunction and ventricular remodelling 1,2. Despite extensive research and improved diagnosis and understanding of the pathogenesis of inflammatory cardiomyopathy, this disorder is still associated with a poor prognosis when complicated by left ventricular (LV) dysfunction, heart failure (HF) or arrhythmia 3. Furthermore, fulminant myocarditis, a rare, sudden and severe cardiac inflammation, is one of the main causes of cardiogenic shock in young adults 4,5. Prompt diagnosis and specific treatment strategies are needed to reduce mortality and the need for heart transplantation in these patients 4,5. Many questions remain unanswered regarding the pathogenesis of inflammatory cardiomyopathy and the role of the viral infection, the immune system, the host genetic background and the environment in disease progression and prognosis. These gaps in knowledge highlight the need for advanced experimental systems that can better model the human immune system and the need to improve the characterization and classification of the patients, for example, with the use of phenomapping and phenomics, which involve detailed evaluation of immune status, viral presence and/or other biomarkers. In this Review, we discuss the available evidence and identify the gaps in our understanding of the pathogenesis, diagnosis, treatment and prognosis of myocarditis and inflammatory cardiomyopathy, appraise the available animal and cell models of these conditions and propose future directions for the field. We discuss the role

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Section: Anti-il-1β and Anti-il-1 Receptor Antibodiesmentioning

confidence: 86%

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions

et al. 2020

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“…Sandwich ELISA experiment was performed according to the manufacturer’s protocol. 56 In brief, 100 μL undiluted supernatant was used to measure absorbance at 450 nM by synergy spectrophotometer (BioTek Instruments). 57 …”

Section: Methodsmentioning

confidence: 99%

“…Total RNA was extracted from cells or mouse heart tissues using TRIzol reagent (15596018; Invitrogen) according to the manufacturer’s instructions. 56 In short, 500 ng total RNA was used to make cDNA by using PrimeScript RT reagent Kit (RR037A; Takara, Japan) according to the manufacturer’s instructions. 65 The resulting cDNA was subjected to real-time PCR using SYBR Premix Ex TaqII (Tli RNaseH Plus) kit (RR820A; Takara) on an Applied Biosystems 7500 Fast Real-Time PCR System (ABI, Torrance, CA, USA).…”

Section: Methodsmentioning

confidence: 99%

SERCA Overexpression Improves Mitochondrial Quality Control and Attenuates Cardiac Microvascular Ischemia-Reperfusion Injury

Tan

Mui

Toan

et al. 2020

Molecular Therapy - Nucleic Acids

119

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Despite significant advances in the treatment of myocardial ischemia-reperfusion (I/R) injury, coronary circulation is a so far neglected target of cardioprotection. In this study, we investigated the molecular mechanisms underlying I/R injury to cardiac microcirculation. Using gene delivery, we analyzed microvascular protective effects of sarcoplasmic/endoplasmic reticulum Ca 2+ -ATPase (SERCA) on the reperfused heart and examined the role of SERCA in regulating mitochondrial quality control in cardiac microvascular endothelial cells (CMECs). Our data showed that SERCA overexpression attenuates lumen stenosis, inhibits microthrombus formation, reduces inflammation response, and improves endothelium-dependent vascular relaxation. In vitro experiments demonstrated that SERCA overexpression improves endothelial viability, barrier integrity, and cytoskeleton assembly in CMECs. Mitochondrial quality control, including mitochondrial fusion, mitophagy, bioenergetics, and biogenesis, were disrupted by I/R injury but were restored by SERCA overexpression. SERCA overexpression also restored mitochondrial quality control by inhibiting calcium overload, inactivating xanthine oxidase (XO), and reducing intracellular/mitochondrial reactive oxygen species (ROS). Administration of exogenous XO or a calcium channel agonist abolished the protective effects of SERCA overexpression on mitochondrial quality control and offset the beneficial effects of SERCA overexpression after cardiac microvascular I/R injury. These findings indicate that SERCA overexpression may be an effective approach to targeting cardiac microvascular I/R injury by regulating calcium/XO/ROS signaling and preserving mitochondrial quality control.

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“…ICAM-1 is an adhesion molecule that allows cells to connect to other cells or to extracellular matrix molecules and plays an important role in inflammatory processes [31]. These factors are known to increase during inflammatory or apoptotic diseases, such as myocarditis, rheumatoid arthritis, diabetes, and systemic lupus erythematosus [32][33][34][35]. In the EIU model, we observed an inflammatory response in the ocular anterior segment, and these inflammatory cytokines were markedly higher than in the control group.…”

Section: Discussionmentioning

confidence: 89%

Synthetic Glucocorticoid-Induced Leucine Zipper Peptide Inhibits Lipopolysaccharide-Induced Ocular Inflammation in Rats

Guo

et al. 2019

Ophthalmic Res

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To demonstrate the anti-inflammatory action of a synthetic glucocorticoid-induced leucine zipper (GILZ 98-134) peptide (GILZ-p) in a model of endotoxin-induced uveitis (EIU) in rats. Methods: The EIU model was induced in Sprague Dawley rats with an intravitreal injection of lipopolysaccharide (LPS). Synthetic GILZ-p was injected intravitreally 6 h after the LPS injection. To evaluate the anti-inflammatory effects of GILZ-p, the inflammatory response in the anterior chamber and iris of the rat eyes was evaluated with a slitlamp microscope on days 0, 1, 2, 3, and 4 after GILZ-p injection. The retinal expression of inflammatory cytokines was measured on days 0, 1, 2, 3, and 4 after GILZ-p injection. Müller cell gliosis was also detected at planned time points after GILZ-p injection. Results: Anterior segment inflammation peaked at 24 h after LPS injection in the EIU model. Compared with the controls, intravitreal GILZ-p significantly suppressed LPS-induced anterior segment inflammation in the EIU rats. The levels of retinal inflammatory factors IL-1β, TNF-α, MCP-1, and ICAM-1 were simultaneously reduced by the intravitreal GILZ-p injection. The expression of vimentin in the EIU retina was significantly reduced by GILZ-p, and the downregulated aquaporin 4 in the EIU retina was significantly restored by GILZ-p. Conclusion: The synthetic GILZ-p inhibited the inflammatory reaction in the EIU model and may have utility in the treatment of inflammatory ocular disease.

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Blocking the IL-1β signalling pathway prevents chronic viral myocarditis and cardiac remodeling

Cited by 85 publications

References 42 publications

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions

Myocarditis and inflammatory cardiomyopathy: current evidence and future directions

SERCA Overexpression Improves Mitochondrial Quality Control and Attenuates Cardiac Microvascular Ischemia-Reperfusion Injury

Synthetic Glucocorticoid-Induced Leucine Zipper Peptide Inhibits Lipopolysaccharide-Induced Ocular Inflammation in Rats

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