Innate immune memory after brain injury drives inflammatory cardiac dysfunction II

Besides the local inflammatory immune response in the brain, stroke also alters systemic immunity. Within the acute and sub-acute phase, the systemic immune response to stroke has been described in detail over last decades. The long-term systemic immunological consequences after stroke are however still elusive. Therefore, a better understanding of these long-lasting chronic effects of stroke on systemic immunity and its impact on remote organ function and secondary comorbidities is needed. Here, we investigated the long-term consequences of stroke on the heart. By performing serial cardiac ultrasound imaging in mice, we found that stroke leads to chronic cardiac dysfunction, which was associated with increased cardiac fibrosis. We found that this phenomenon was driven by an increased infiltration of bone marrow-derived monocytes into the heart after stroke, which results in increased expression of metalloproteinase-9 (Mmp9) by cardiac monocytes/macrophages. To further investigate the translational relevance of this post-stroke cardiac phenotype, we analyzed heart samples from patients who died due to stroke and control patients and performed bulk mRNA sequencing.