Modulation of Rage and CD147 in Cerebral Amyloid Angiopathy <i>in vitro</i>

Abstract

Introduction. In the study of Alzheimer’s disease (AD), the cause-and-effect relationship between neurodegenerative changes and the accompanying amyloid angiopathy is becoming increasingly important. The accumulated clinical data indicates that an important contribution to the pathogenesis of AD is made by neurovascular unit dysfunction, including disruption in permeability of the blood-brain barrier (BBB), microcirculation, and metabolic coupling of cells.Aim. To study the molecular mechanisms of disturbed brain microcirculation and the structural and functional integrity of the BBB in experimental models of AD in vitro under the modulation of CD147 and RAGE.Materials and methods. The study was carried out on C57BL/6 mice. First, we formed an AD model in animals of the experimental group. Then, we isolated and cultured primary cells of the brain, modulated the activity of CD147 and RAGE in endothelial cells using siRNA CD147, siRNA RAGE, cyclophilin A and Aβ1-42, and formed a BBB model in vitro. Further, we assessed transendothelial electrical resistance in the BBB model in vitro, registered the marker molecules of angiogenesis and analyzed the expression of APP in endothelial cells. Statistical processing of the obtained data was carried out using the methods of nonparametric statistics: the Mann – Whitney U test for comparing independent samples and the Wilcoxon test for comparing dependent samples. The level of statistical significance of differences was p ≤ 0.05.Results and discussion. Knockdown of RAGE led to a statistically significant increase in TEER, an intensification of neoangiogenesis, and a decrease in the level of APP expression. At the same time, although CD147 knockdown led to an increase in TEER, it also led to controversial effects on angiogenesis and an increase in APP expression.Conclusion. Analyzing the data obtained, it can be concluded that RAGE and CD147 silencing in the cells of cerebral microvessels can become a promising method for reducing their pathological permeability.