The effects of inflammation on cardiovascular system
Project title: UNIRI PROJECTS BY YOUNG RESEARCHERS AND RESEARCHERS RETURNEES - The effects of inflammation on cardiovascular system
Funding source: University of Rijeka
Project code: uniri-mz-25-63
Coordinator: Marko Šustić, MD, PhD
Total funding: 27.804,16 €
Project implementation period: 01.10.2025. - 31.01.2029.
Brief description: In recent decades, physiological and pathological processes in the heart have been increasingly looked upon through the lens of the immune system, giving birth to the new field of cardioimmunology. Several lines of research have indicated that latent cytomegalovirus infection (CMV) can have major impact on the functioning of the immune system of mammals. Human data have shown that cytomegalovirus serostatus was a single largest non-genetic determinant of an immune phenotype of an individual. In a murine model of bacterial infection, it was shown that CMV latency conferred protection in the context of acute pneumonia via modulation of innate immunity in the lungs. Whether similar protective or detrimental effects of latent CMV infection exist in cardiac physiology and pathology has not been investigated. To investigate the long-term effects of latent viral infection, we used murine cytomegalovirus (MCMV) as a model. In our previous studies, we have identified widespread changes in the cardiac leukocyte composition in the hearts of mice latently infected with MCMV. Moreover, transcriptome analysis revealed extensive upregulation of proinflammatory genes, and, importantly, simultaneous downregulation of genes associated with oxidative phosphorylation.
The aim of this study is to perform mitochondrial cellular respiration experiments to investigate the presence of energy production defects in the hearts MCMV infected mice. As we observed extensive infiltration and long-term maintenance of CD8 T cell in the cardiac tissue after MCMV infection, we also aim to determine whether these T cells recognize auto-antigens derived from cardiac proteins, thereby potentially leading to autoimmune response against cardiac tissue. Finally, as cardiovascular and renal systems have closely interlinked physiological functions and the pathological perturbations in one of them always effect the other, we aim to investigate the inflammatory changes induced by MCMV infection in the kidneys.
