TY - JOUR
T1 - Transient atrial inflammation in a murine model of Coxsackievirus B3-induced myocarditis
AU - Wu, Linghe
AU - Fiet, Mitchell D.
AU - Raaijmakers, Daan R.
AU - Woudstra, Linde
AU - van Rossum, Albert C.
AU - Niessen, Hans W.M.
AU - Krijnen, Paul A.J.
N1 - Funding Information: This study was funded by a grant from the Institute for Cardiovascular Research (ICaR‐VU), Amsterdam, the Netherlands. Linghe Wu was funded by a grant from the Chinese Scholarship Council (CSC, 201708260020). Publisher Copyright: © 2022 The Authors. International Journal of Experimental Pathology published by John Wiley & Sons Ltd on behalf of Company of the International Journal of Experimental Pathology (CIJEP).
PY - 2022/8
Y1 - 2022/8
N2 - Atrial dysfunction is a relatively common complication of acute myocarditis, although its pathophysiology is unclear. There is limited information on myocarditis-associated histological changes in the atria and how they develop in time. The aim of this study therefore was to investigate inflammation, fibrosis and viral genome in the atria in time after mild CVB3-induced viral myocarditis (VM) in mice. C3H mice (n = 68) were infected with 105 PFU of Coxsackievirus B3 (CVB3) and were compared with uninfected mice (n = 10). Atrial tissue was obtained at days 4, 7, 10, 21, 35 or 49 post-infection. Cellular infiltration of CD45+ lymphocytes, MAC3+ macrophages, Ly6G+ neutrophils and mast cells was quantified by (immuno)histochemical staining. The CVB3 RNA was determined by in situ hybridization, and fibrosis was evaluated by elastic van Gieson (EvG) staining. In the atria of VM mice, the numbers of lymphocytes on days 4 and 7 (p <.05) and days 10 (p <.01); macrophages on days 7 (p <.01) and 10 (p <.05); neutrophils on days 4 (p <.05); and mast cells on days 4 and 7 (p <.05) increased significantly compared with control mice and decreased thereafter to basal levels. No cardiomyocyte death was observed, and the CVB3 genome was detected in only one infected mouse on Day 4 post-infection. No significant changes in the amount of atrial fibrosis were found between VM and control mice. A temporary increase in inflammation is induced in the atria in the acute phase of CVB3-induced mild VM, which may facilitate the development of atrial arrhythmia and contractile dysfunction.
AB - Atrial dysfunction is a relatively common complication of acute myocarditis, although its pathophysiology is unclear. There is limited information on myocarditis-associated histological changes in the atria and how they develop in time. The aim of this study therefore was to investigate inflammation, fibrosis and viral genome in the atria in time after mild CVB3-induced viral myocarditis (VM) in mice. C3H mice (n = 68) were infected with 105 PFU of Coxsackievirus B3 (CVB3) and were compared with uninfected mice (n = 10). Atrial tissue was obtained at days 4, 7, 10, 21, 35 or 49 post-infection. Cellular infiltration of CD45+ lymphocytes, MAC3+ macrophages, Ly6G+ neutrophils and mast cells was quantified by (immuno)histochemical staining. The CVB3 RNA was determined by in situ hybridization, and fibrosis was evaluated by elastic van Gieson (EvG) staining. In the atria of VM mice, the numbers of lymphocytes on days 4 and 7 (p <.05) and days 10 (p <.01); macrophages on days 7 (p <.01) and 10 (p <.05); neutrophils on days 4 (p <.05); and mast cells on days 4 and 7 (p <.05) increased significantly compared with control mice and decreased thereafter to basal levels. No cardiomyocyte death was observed, and the CVB3 genome was detected in only one infected mouse on Day 4 post-infection. No significant changes in the amount of atrial fibrosis were found between VM and control mice. A temporary increase in inflammation is induced in the atria in the acute phase of CVB3-induced mild VM, which may facilitate the development of atrial arrhythmia and contractile dysfunction.
KW - Coxsackievirus B3
KW - atria
KW - in situ hybridization
KW - inflammation
KW - viral myocarditis
UR - http://www.scopus.com/inward/record.url?scp=85127384860&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/iep.12438
DO - https://doi.org/10.1111/iep.12438
M3 - Article
C2 - 35363404
SN - 0959-9673
VL - 103
SP - 149
EP - 155
JO - International journal of experimental pathology
JF - International journal of experimental pathology
IS - 4
ER -