Zhihan Wang, University of British Columbia

Zhihan Wang (UBC/HLI), Dr. Yasir Mohamud (UBC/HLI), Dr. Amrit Singh (UBC/HLI), Dr. Tao Sun (HLI), Dr. Honglin Luo*(UBC/HLI))

Damaging & Spreading

Myocarditis, often triggered by viral infections such as enteroviruses, can progress to dilated cardiomyopathy and heart failure, particularly in males. Analysis of the GSE35182 GEO dataset revealed the circadian-associated repressor of transcription (CIART) as a potential factor in sex-based disease severity differences, due to its unique upregulation in males. The influence of CIART on viral myocarditis, however, remains unexplored. This project aims to investigate the role and regulation of CIART in viral myocarditis, to address the hypothesis that CIART's upregulation could worsen the condition in males, presenting a novel treatment avenue. This study investigates the role of CIART in viral myocarditis progression, focusing on sex-specific expression, molecular mechanisms, and therapeutic implications. We will examine CIART expression in male and female mice with Coxsackievirus B3 (CVB3)-induced myocarditis using qRT-PCR and immunohistochemistry, aiming to link CIART levels with disease severity. The research will explore molecular pathways affected by CIART through transcriptomic and proteomic analyses and validate its regulatory role via in vitro models and genetic engineering. Finally, we will test CIART modulation's therapeutic potential in a cardiac-specific CIART-deficient mouse model, assessing its impact on myocardial inflammation, immune response, and cardiac function. In summary, our study found a notable sex-based difference in CIART expression after CVB3 infection, with males showing increased and females decreased CIART levels. By utilizing online protein-protein interaction network tools, we also identified hub genes, including Laptm5, Cfp, and Myo1g. These initial results highlight the potential of developing sex-specific treatment for viral myocarditis by targeting CIART, particularly in males.