Vitamin D receptor activation regulates microglia polarization and oxidative stress in spontaneously hypertensive rats and angiotensin II-exposed microglial cells: Role of renin-angiotensin system.
Level 5 - mechanism / opinion, no new human data
Preclinical animal model (SHR rats) and in vitro cell experiment
PubMed 31421410 · doi:10.1016/j.redox.2019.101295
What was done
Researchers investigated the neuroprotective mechanisms of vitamin D receptor (VDR) activation in spontaneously hypertensive rats (SHR) and angiotensin II (Ang II)-treated BV2 microglial cells. They evaluated the effects of calcitriol on prefrontal cortex neuronal death, microglial polarization (M1 versus M2 markers), proinflammatory cytokines, oxidative stress (NADPH-oxidase/Nox activity and ROS), and classical versus alternative renin-angiotensin system (RAS) pathways (ACE/Ang II/AT1 versus ACE2/Ang(1-7)/MasR), using the MasR antagonist A779 to test pathway dependence.
What was found
The abstract reports directional changes without exact numerical values or effect sizes. In SHR prefrontal cortex, calcitriol induced VDR expression, reduced neural death, suppressed M1 microglia polarization, and enhanced M2 polarization alongside reduced proinflammatory cytokine expression. Calcitriol markedly decreased Ang II production and substantially upregulated the ACE2/Ang(1-7)/MasR axis (elevating ACE2, MasR, and Ang(1-7)), while exerting non-significant reductions on ACE and AT1. Calcitriol also attenuated Nox overactivation and oxidative stress. In BV2 microglial cells, calcitriol similarly stimulated ACE2/MasR, blunted Ang II-induced Nox activation and ROS production, and promoted M2 polarization; these neuroprotective and antioxidant effects were blocked by co-treatment with the MasR antagonist A779.
Why it matters
This study delineates a mechanistic link between vitamin D signaling and the neuroprotective ACE2/Ang(1-7)/MasR counter-regulatory arm of the brain renin-angiotensin system, suggesting a potential pathway to target neuroinflammation and oxidative stress in hypertension-associated brain injury.
Limits
The study is restricted to an animal model and an immortalized microglial cell line, precluding direct clinical translation to human hypertensive neurodegeneration. Exact sample sizes, drug dosages, quantitative metrics, and functional behavioral or cognitive outcomes were not detailed in the abstract.
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