The effects of NK4 on viral myocarditis mice
Difei Shen1, Qizhu Tang, Zhengrong Huang
1Department of Cardiology, Renmin Hospital, Wuhan University, Wuhan, P.R. China.
Abstract:
NK4 may be a promising agent to inhibit tumor invasion and metastasis. To observe the effects of NK4 on the cardiovascular system with pathological injury and to discuss the mechanism, we established an experimental model of viral myocarditis (VCM) by coxsackievirus B3 infection in Balb/c mice on Day 0 and administered NK4 twice daily to the VCM and control mice from Day 20 to Day 45. We then evaluated the cardiac function by means of ultrasonic inspection. Hepatocyte growth factor, TNF (tumor necrosis factor)-alpha, and angiotensin II levels in the myocardial tissue were measured with enzyme-linked immunosorbent assay. Myocardium histopathology was examined with hematoxylin and eosin stain. Collagen deposition of the myocardium was detected through Masson staining. Microvessel staining with the RECA antibody and apoptosis detection with terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling were performed in the myocardium. The changes in MMP3 (matrix metalloproteinase 3), MMP9, TIMP1 (tissue inhibitor of metalloproteinase 1), and TGF (transforming growth factor)-beta1 expression in the myocardium were measured by reverse-transcriptase polymerase chain reaction. We found that NK4 intervention increased TGF-beta and angiotensin II expression, suppressed MMPs, improved the activities of TIMPs, and then promoted collagen deposition in the myocardium. NK4 intervention also decreased the microvessels' density and increased the apoptotic cell count in the myocardia of VCM mice. However, we did not observe the obvious changes in the myocardia of control mice after NK4 intervention. These data suggest that NK4 made negative impacts on the restoration of cardiac function and the recovery from VCM in the experimental mice.
Insights
NK4 negatively impacted cardiac function recovery in viral myocarditis mice by increasing fibrosis and apoptosis. This suggests NK4 may not be suitable for treating cardiovascular conditions involving pathological injury.
Area of Science:
- Cardiovascular Science
- Oncology
- Immunology
Background:
- NK4 is explored for its potential to inhibit tumor invasion and metastasis.
- Viral myocarditis (VCM) involves pathological injury to the cardiovascular system.
- Understanding NK4's effects on cardiac recovery is crucial.
Purpose of the Study:
- To investigate the impact of NK4 on cardiovascular function during viral myocarditis.
- To elucidate the underlying mechanisms of NK4's effects in a VCM model.
Main Methods:
- Established a viral myocarditis model in Balb/c mice using coxsackievirus B3.
- Administered NK4 to VCM and control groups, assessing cardiac function via ultrasound.
- Analyzed myocardial tissue for growth factors, inflammatory markers, histopathology, collagen deposition, microvessel density, apoptosis, and gene expression (MMPs, TIMPs, TGF-β1).
Main Results:
- NK4 intervention increased TGF-beta and angiotensin II levels, suppressed matrix metalloproteinases (MMPs), enhanced tissue inhibitor of metalloproteinases (TIMPs) activity, and promoted myocardial collagen deposition.
- NK4 reduced microvessel density and increased apoptosis in VCM mice.
- No significant changes were observed in control mice treated with NK4.
Conclusions:
- NK4 demonstrated negative effects on cardiac function restoration and VCM recovery in experimental mice.
- These findings suggest NK4 may adversely impact the cardiovascular system in pathological injury contexts.
