Angiotensin-II drives changes in microglia–vascular interactions in rats with heart failure

• Published in: Communications biology Vol. 7; no. 1; p. 1537
• Main Authors: Althammer, Ferdinand, Roy, Ranjan K., Kirchner, Matthew K., Podpecan, Yuval, Helen, Jemima, McGrath, Shaina, Lira, Elba Campos, Stern, Javier E.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19-11-2024; Nature Publishing Group
• Subjects: 14/1; 14/19; 14/32; 38; 38/77; 59; 631/378/2596/1953; 64; 692/4019/592/75/230; Angiotensin; Angiotensin II; Autonomic nervous system; Biomedical and Life Sciences; Blood flow; Blood levels; Blood vessels; Blood-brain barrier; Capillaries; Cardiovascular diseases; Cell activation; Central nervous system; Cerebral blood flow; Congestive heart failure; Heart diseases; Heart failure; Hippocampus; Inflammation; Ischemia; Life Sciences; Microglia; Microvasculature; Pathophysiology; Therapeutic targets
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-024-07229-8

Activation of microglia, the resident immune cells of the central nervous system, leading to the subsequent release of pro-inflammatory cytokines, has been linked to cardiac remodeling, autonomic disbalance, and cognitive deficits in heart failure (HF). While previous studies emphasized the role of hippocampal Angiotensin II (AngII) signaling in HF-induced microglial activation, unanswered mechanistic questions persist. Evidence suggests significant interactions between microglia and local microvasculature, potentially affecting blood–brain barrier integrity and cerebral blood flow regulation. Still, whether the microglial-vascular interface is affected in the brain during HF remains unknown. Using a well-established ischemic HF rat model, we demonstrate the increased abundance of vessel-associated microglia (VAM) in HF rat hippocampi, along with an increased expression of AngII AT1a receptors. Acute AngII administration to sham rats induced microglia recruitment to brain capillaries, along with increased expression of TNFα. Conversely, administering an AT1aR blocker to HF rats prevented the recruitment of microglia to blood vessels, normalizing their levels to those in healthy rats. These results highlight the critical importance of a rather understudied phenomenon (i.e., microglia-vascular interactions in the brain) in the context of the pathophysiology of a highly prevalent cardiovascular disease, and unveil novel potential therapeutic avenues aimed at mitigating neuroinflammation in cardiovascular diseases.
This study shows changes in microglia-vascular interactions in the context of heart failure, which unveils a novel potential therapeutic target for mitigating neuroinflammation in cardiovascular diseases.