Cardiovascular research · 2023
Neutrophil inhibition improves acute inflammation in a murine model of viral myocarditis.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
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Carai Paolo, González Laura Florit, Van Bruggen Stijn, Spalart Valerie, De Giorgio Daria, Geuens Nadéche, Martinod Kimberly, Jones Elizabeth Anne Vincent, Heymans Stephane
Аннотация
AIMS: Viral myocarditis (VM) is an inflammatory pathology of the myocardium triggered by a viral infection that may cause sudden death or heart failure (HF), especially in the younger population. Current treatments only stabilize and improve cardiac function without resolving the underlying inflammatory cause. The factors that induce VM to progress to HF are still uncertain, but neutrophils have been increasingly associated with the negative evolution of cardiac pathologies. The present study investigates the contribution of neutrophils to VM disease progression in different ways.
METHODS AND RESULTS: In a coxsackievirus B3- (CVB3) induced mouse model of VM, neutrophils and neutrophil extracellular traps (NETs) were prominent in the acute phase of VM as revealed by enzyme-linked immunosorbent assay analysis and immunostaining. Anti-Ly6G-mediated neutrophil blockade starting at model induction decreased cardiac necrosis and leucocyte infiltration, preventing monocyte and Ly6CHigh pro-inflammatory macrophage recruitment. Furthermore, genetic peptidylarginine deiminase 4-dependent NET blockade reduced cardiac damage and leucocyte recruitment, significantly decreasing cardiac monocyte and macrophage presence. Depleting neutrophils with anti-Ly6G antibodies at 7 days post-infection, after the acute phase, did not decrease cardiac inflammation.
CONCLUSION: Collectively, these results indicate that the repression of neutrophils and the related NET response in the acute phase of VM improves the pathological phenotype by reducing cardiac inflammation.
METHODS AND RESULTS: In a coxsackievirus B3- (CVB3) induced mouse model of VM, neutrophils and neutrophil extracellular traps (NETs) were prominent in the acute phase of VM as revealed by enzyme-linked immunosorbent assay analysis and immunostaining. Anti-Ly6G-mediated neutrophil blockade starting at model induction decreased cardiac necrosis and leucocyte infiltration, preventing monocyte and Ly6CHigh pro-inflammatory macrophage recruitment. Furthermore, genetic peptidylarginine deiminase 4-dependent NET blockade reduced cardiac damage and leucocyte recruitment, significantly decreasing cardiac monocyte and macrophage presence. Depleting neutrophils with anti-Ly6G antibodies at 7 days post-infection, after the acute phase, did not decrease cardiac inflammation.
CONCLUSION: Collectively, these results indicate that the repression of neutrophils and the related NET response in the acute phase of VM improves the pathological phenotype by reducing cardiac inflammation.