Key result
Obese ZSF1 rats developed progressive neurovascular dysfunction and cognitive impairment associated with reduced Trpv4 and Klf2 expression in cerebral microvessels compared to Lean rats.
Why the study?
Vascular cognitive impairment shares risk factors with HFpEF, but research often relies on single-stimulus models rather than combined risk factors.
Population
Male Lean and Obese ZSF1 rats
Comparison
Obese vs Lean rats
Design
Animal model longitudinal study
Follow-up
34-35 weeks
Authors
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Potential Trpv4/Klf2 targets for obesity-related cognitive decline; hypothesis-generating and leaves open human translation.
In a rat model of HFpEF, progressive neurovascular dysfunction and cognitive impairment are associated with the downregulation of vasoprotective genes Trpv4 and Klf2 in cerebral microvessels.
Lambrichts et al. (2025) studied Heart failure with preserved ejection fraction (HFpEF) and Vascular cognitive impairment (VCI) (n=69). Obese ZSF1 phenotype (HFpEF model) vs. Lean ZSF1 rats was evaluated on Neurovascular coupling, cognitive performance, and Trpv4/Klf2 expression. Obese ZSF1 rats developed progressive neurovascular dysfunction and cognitive impairment associated with reduced Trpv4 and Klf2 expression in cerebral microvessels compared to Lean rats.
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