Clin Res Cardiol (2022). https://doi.org/10.1007/s00392-022-02087-y
Effect of bacterial pneumonia on endothelial regeneration and immune cell differentiation after vascular injury in mice
P. Ramezani Rad1, V. Nageswaran1, L. Reinshagen1, N. Kränkel1, L. Peters2, S. Simmons3, W. Kübler4, U. Behrendt5, M. Brack5, M. Witzenrath5, U. Landmesser1, A. Haghikia1
1CC 11: Med. Klinik für Kardiologie, Charité - Universitätsmedizin Berlin, Berlin; 2CC2: Institut für Physiologie, CCO, Charité - Universitätsmedizin Berlin, Berlin; 3Labor für Lungenkreislaufforschung, Nachwuchsgruppe Immunodynamik, Institut für Physiologie, Charité - Universitätsmedizin Berlin, Berlin; 4Institut für Physiologie, Deutsches Herzzentrum Berlin, Berlin; 5CC12: Med. Klinik m. S. Infektiologie und Pneumologie, Charité - Universitätsmedizin Berlin, Berlin;

Background and aims
Pneumonia is associated with an increased incidence of adverse cardiovascular events, impacting clinical long-term outcome. However, the underlying patho-mechanisms of how pneumonia increases cardiovascular risk are only poorly understood. In this study, we investigated the effect of bacterial pneumonia on immune cell differentiation, plasma proteome profile and vascular regeneration after injury in a mouse carotid injury model.

Methods and results

C57BL/6 mice were infected with Streptococcus pneumoniae (TIGR4) or PBS and treated with ampicillin, starting 24 hours post infection (p.i.). On day 7 p.i. carotid artery injury (CI) was induced using a bipolar microforceps. Three days post-CI (10 days p.i.) vascular regeneration and re-endothelialization were determined by Evans blue staining. Our results showed that infection with Streptococcus pneumoniae impaired wound healing as compared to control animals. Ten days after infection the spleen, bone marrow and whole blood samples were collected for immune cell phenotyping by flow cytometric analysis. Monocytes subsets (Ly6Chi and Ly6Clow) and T cell distribution (Th, Th1, Th17, naive and memory Th cells, cytotoxic T cells, Tc1 and Tregs) were analysed in infected mice as compared to the control group (PBS). In particular, a significant increase in Ly6Clow and a decrease in Ly6Chi was observed in whole blood upon bacterial infection. Moreover, a significant increase in pro-atherogenic Th1 cells was detected in the spleen of infected mice. Furthermore, proteome profiling (Olink) of the plasma showed a significant increase in glucagon levels in mice with bacterial infection.

Conclusions

Our findings demonstrate impaired endothelial repair after injury upon bacterial pneumonia. This was accompanied by increased splenic Th1 cell differentiation, decreased circulatory Ly6Chi levels and elevated plasma glucagon levels, suggesting a distinct immuno-metabolic pathway, which may contribute to the development of vascular disease and elevated pneumonia-related cardiovascular risk. 
https://dgk.org/kongress_programme/ht2022/aBS658.html