Hypertriglyceridemia is not only a serious risk factor in the development of cardiovascular
diseases, but it is linked to neurodegeneration, too. Previously, we generated transgenic
mice overexpressing the human APOB-100 protein, a mouse model of human atherosclerosis.
In this model we observed high plasma levels of triglycerides, oxidative stress, tau
hyperphosphorylation, synaptic dysfunction, cognitive impairment, increased neural
apoptosis and neurodegeneration. Neurovascular dysfunction is recognized as a key
factor in the development of neurodegenerative diseases, but the cellular and molecular
events linking cerebrovascular pathology and neurodegeneration are not fully understood.
Our aim was to study cerebrovascular changes in APOB-100 transgenic mice. We described
the kinetics of the development of chronic hypertriglyceridemia in the transgenic
animals. Increased blood-brain barrier permeability was found in the hippocampus of
APOB-100 transgenic mice which was accompanied by structural changes. Using transmission
electron microscopy, we detected changes in the brain capillary endothelial tight
junction structure and edematous swelling of astrocyte endfeet. In brain microvessels
isolated from APOB-100 transgenic animals increased Lox-1, Aqp4, and decreased Meox-2,
Mfsd2a, Abcb1a, Lrp2, Glut-1, Nos2, Nos3, Vim, and in transgenic brains reduced Cdh2
and Gfap-σ gene expressions were measured using quantitative real-time PCR. We confirmed
the decreased P-glycoprotein (ABCB1) and vimentin expression related to the neurovascular
unit by immunostaining in transgenic brain sections using confocal microscopy. We
conclude that in chronic hypertriglyceridemic APOB-100 transgenic mice both functional
and morphological cerebrovascular pathology can be observed, and this animal model
could be a useful tool to study the link between cerebrovascular pathology and neurodegeneration.