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

Ferdinand Althammer1,2, Ranjan K Roy1,3, Matthew K Kirchner1,3

  • 1Center for Neuroinflammation and Cardiometabolic Diseases, Georgia State University, Atlanta, GA, USA.

Communications Biology
|November 20, 2024
PubMed

Insights

Heart failure triggers neuroinflammation by increasing vessel-associated microglia in the brain. Blocking Angiotensin II AT1a receptors reduces this microglial recruitment, offering a potential therapeutic target for cardiovascular diseases.

Area of Science:

  • Neuroscience
  • Cardiovascular Science
  • Immunology

Background:

  • Microglial activation and pro-inflammatory cytokine release in the central nervous system are linked to heart failure (HF) complications.
  • Previous research focused on hippocampal Angiotensin II (AngII) signaling in HF-induced microglial activation, but the underlying mechanisms and neurovascular interactions remain unclear.
  • The interplay between microglia and the brain's microvasculature, affecting blood-brain barrier integrity and cerebral blood flow, is understudied in the context of HF.

Purpose of the Study:

  • To investigate the impact of heart failure on the microglial-vascular interface in the brain.
  • To explore the role of Angiotensin II (AngII) signaling in HF-induced changes in microglia-vascular interactions.
  • To identify potential therapeutic targets for mitigating neuroinflammation in cardiovascular diseases.

Main Methods:

  • Utilized a well-established ischemic heart failure (HF) rat model.
  • Quantified vessel-associated microglia (VAM) and AngII AT1a receptor expression in the hippocampus.
  • Administered AngII to sham rats and an AT1a receptor blocker to HF rats to assess microglial responses and TNFα expression.

Main Results:

  • Demonstrated increased abundance of vessel-associated microglia (VAM) in the hippocampi of HF rats.
  • Observed increased expression of AngII AT1a receptors in the brains of HF rats.
  • Showed that AngII administration induced microglial recruitment to brain capillaries and TNFα expression, while AT1aR blockade in HF rats prevented this recruitment.

Conclusions:

  • Heart failure leads to increased microglia-vascular interactions in the brain, characterized by the recruitment of microglia to blood vessels.
  • Angiotensin II (AngII) signaling, via AT1a receptors, plays a critical role in mediating HF-induced microglial recruitment to the brain vasculature.
  • Targeting microglia-vascular interactions and AngII signaling presents a novel therapeutic strategy for managing neuroinflammation associated with cardiovascular diseases.

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