Changes in Microglia-Vascular Interactions in the Brain of Rats with Heart Failure

Recent studies have shown microglia, the tissue-resident macrophages of the central nervous system, can interact with the local microvasculature, suggesting their potential ability to alter the blood–brain barrier (BBB) permeability and influence neurovascular coupling. Our previous work has shown that in the hippocampus, systemic Angiotensin II (AngII) signaling can drive microglia to shift to a reactive state in heart failure (HF) rats, contributing in turn to hippocampal neuroinflammation and cognitive deficits in HF (Althammer, F., Et al., 2023); however, whether microglial-vascular interactions are affected in the brain during HF remains unknown. In this study, using an ischemic HF rat model, we aimed to characterize any changes in microglial-vascular interactions induced by this disease state. We hypothesized that HF would promote a greater number of microglia contacting hippocampal vasculature. Indeed, we found an increase in the percentage of vessel-associated microglia (VAM) (110% increase, p < 0.0001), as well as an increase in microglial expression of AngII AT1a receptors in the hippocampus of HF rats (~200% increase, p < 0.0001). Furthermore, acute AngII administration to sham rats was sufficient to induce microglia recruitment to hippocampal capillaries (80% increase, p < 0.0001), while administration of an AT1aR blocker to HF rats diminished VAMs (51% decrease, p < 0.0001) to similar levels observed in sham rats. These findings demonstrate a disease-state-dependent change in the association between microglia and local blood vessels through the recruitment of microglia to the perivascular space by a circulating hormone (AngII). Because microglia are transcriptionally heterogeneous between brain regions and likely, have specialized functions relative to their local environments and neuronal subpopulations, we are currently exploring changes in the microglial-vascular interface in hypothalamic brain regions, where neuroinflammation and changes in BBB integrity have been shown to contribute to neurohumoral activation and morbidity/mortality in this prevalent cardiovascular disease. Funding received from 1R01HL162575-01 and DFG Emmy Noether starting grant AL 2466/2-1 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.