Abstract
Protein kinase B2 (AKT2) is involved in various cardiomyocyte signaling processes, including those important for survival and metabolism. Coxsackievirus B3 (CVB3) is one of the most common pathogens that cause myocarditis in humans. The role of AKT2 in CVB3 infection is not yet well understood. We used a cardiac-specific AKT2 knockout (KO) mouse to determine the role of AKT2 in CVB3-mediated myocarditis. CVB3 was injected intraperitoneally into wild-type (WT) and KO mice. The mice’s survival rate was recorded: survival in KO mice was significantly decreased compared with WT mice (WT vs. KO: 73.3 vs. 27.1%). Myocardial damage and inflammation were significantly increased in the hearts of KO mice compared with those of WT mice. Moreover, from surface ECG, AKT2 KO mice showed a prolonged atria and ventricle conduction time (PR interval, WT vs. KO: 47.27 ± 1.17 vs. 64.79 ± 7.17 ms). AKT2 deletion induced severe myocarditis and cardiac dysfunction due to CVB3 infection. According to real-time PCR, the mRNA level of IL-1, IL-6, and TNF-α decreased significantly in KO mice compared with WT mice on Days 5 after infection. In addition, innate immune response antiviral effectors, Type I interferon (interferon-α and β), and p62, were dramatically suppressed in the heart of KO mice. In particular, the adult cardiac myocytes isolated from the heart showed high induction of TLR4 protein in KO mice in comparison with WT. AKT2 deletion suppressed the activation of Type I interferon and p62 transcription in CVB3 infection. In cardiac myocytes, AKT2 is a key signaling molecule for the heart from damage through the activation of innate immunity during acute myocarditis.
Highlights
IntroductionMyocardial damage and inflammation were significantly increased in the hearts of KO mice compared with those of WT mice
Most enterovirus infections are subclinical, acute myocardial inflammation triggered by these infections can induce severe arrhythmias and sudden cardiac death or may lead to the development of myocarditis and dilated cardiomyopathy [1,2,3]
AKT2 and AKT3 mRNA levels decreased by about 80% and 55% in KO mouse hearts compared with WT hearts, indicating that
Summary
Myocardial damage and inflammation were significantly increased in the hearts of KO mice compared with those of WT mice. AKT2 deletion induced severe myocarditis and cardiac dysfunction due to CVB3 infection. AKT2 deletion suppressed the activation of Type I interferon and p62 transcription in CVB3 infection. AKT2 is a key signaling molecule for the heart from damage through the activation of innate immunity during acute myocarditis. Most enterovirus infections are subclinical, acute myocardial inflammation triggered by these infections can induce severe arrhythmias and sudden cardiac death or may lead to the development of myocarditis and dilated cardiomyopathy [1,2,3]. Reported that TLR4-deficient mice are more resistant to CVB3 infection and have decreased inflammatory responses, viral replication, and myocarditis than wild-type mice [11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
