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Myocardial Infarction in Neonatal Mice, A Model of Cardiac Regeneration
Published on: May 24, 2016
Coxsackievirus A2 Leads to Heart Injury in a Neonatal Mouse Model
Wangquan Ji1, Peiyu Zhu1, Ruonan Liang1
1Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001, China.
Insights
Coxsackievirus A2 (CVA2) causes heart injury in neonatal mice by replicating in heart tissue and triggering inflammation. This viral infection disrupts cell interactions and activates key inflammatory pathways, leading to cardiac damage.
Area of Science:
- Virology
- Cardiology
- Immunology
Background:
- Coxsackievirus A2 (CVA2) is a pathogen linked to hand, foot, and mouth disease (HFMD) and herpangina outbreaks globally.
- Severe CVA2 infections can lead to heart injury, a potential cause of mortality, but the underlying mechanisms remain unclear.
Purpose of the Study:
- To investigate the mechanisms of Coxsackievirus A2-induced heart injury using a neonatal mouse model.
- To elucidate the role of viral replication, matrix metalloproteinases, and inflammatory responses in CVA2 cardiotoxicity.
Main Methods:
- Neonatal mice were infected with CVA2 to establish a model of viral heart injury.
- Detected CVA2 replication and apoptosis in cardiac tissues.
- Assessed levels of cardiac enzymes (AST, LDH), matrix metalloproteinases (MMP3, MMP8, MMP9), growth factors (CTGF), inhibitors (TIMP4), inflammatory cytokines (TNF-α, IL-1β, IL6, MCP-1), and activated signaling pathways (PI3K-AKT, MAPK, NF-κB).
Main Results:
- CVA2 replicated in heart tissues, leading to increased apoptosis and elevated AST and LDH levels.
- Disruption of cell-matrix interactions was observed, with increased MMPs, CTGF, and TIMP4.
- Significant infiltration of leukocytes and elevated expression of inflammatory cytokines and activated inflammatory signaling pathways (PI3K-AKT, MAPK, NF-κB) were noted in infected hearts.
Conclusions:
- CVA2 infection induces heart injury in neonatal mice.
- Mechanisms involve viral replication, altered matrix metalloproteinase activity, and pronounced inflammatory responses, including cytokine activation and signaling pathway engagement.
Abstract:
Coxsackievirus A2 (CVA2) has emerged as an active pathogen that has been implicated in hand, foot, and mouth disease (HFMD) and herpangina outbreaks worldwide. It has been reported that severe cases with CVA2 infection develop into heart injury, which may be one of the causes of death. However, the mechanisms of CVA2-induced heart injury have not been well understood. In this study, we used a neonatal mouse model of CVA2 to investigate the possible mechanisms of heart injury. We detected CVA2 replication and apoptosis in heart tissues from infected mice. The activity of total aspartate transaminase (AST) and lactate dehydrogenase (LDH) was notably increased in heart tissues from infected mice. CVA2 infection also led to the disruption of cell-matrix interactions in heart tissues, including the increases of matrix metalloproteinase (MMP)3, MMP8, MMP9, connective tissue growth factor (CTGF) and tissue inhibitors of metalloproteinases (TIMP)4. Infiltrating leukocytes (CD45+ and CD11b+ cells) were observed in heart tissues of infected mice. Correspondingly, the expression levels of inflammatory cytokines in tissue lysates of hearts, including tumor necrosis factor alpha (TNF-α), interleukin-1beta (IL-1β), IL6 and monocyte chemoattractant protein-1 (MCP-1) were significantly elevated in CVA2 infected mice. Inflammatory signal pathways in heart tissues, including phosphatidylinositol 3-kinase (PI3K)-AKT, mitogen-activated protein kinases (MAPK) and nuclear factor kappa B (NF-κB), were also activated after infection. In summary, CVA2 infection leads to heart injury in a neonatal mouse model, which might be related to viral replication, increased expression levels of MMP-related enzymes and excessive inflammatory responses.
