Transcriptomic analyses reveal proinflammatory activation of human brain microvascular endothelial cells by aging-associated peptide medin and reversal by nanoliposomes

Global transcriptional changes induced by medin, Aβ, and NL in HBMVECs

To investigate molecular impact of medin on HBMVECs, three independent sets of seven treatment groups of HBMVECs were prepared and analyzed by RNA-seq, which included cells treated for 20 h with either Vehicle (culture media), Medin (5 µM, a physiologic concentration found in human tissues^4,8), Scrambled Medin (scrMedin, 5 µM), Aβ(1-42) (2 µM, biologically relevant dose that induced endothelial dysfunction in human tissue¹³), NL (300 µg/mL, dose that reversed medin-induced endothelial dysfunction⁴) and co-treatment groups of Medin + Aβ and Medin + NL. After batch effect correction, Principal Component Analysis (PCA) identified an outlier within the scrMedin group, which was excluded from further analysis (Supplement Fig. 1). The gene expression results of each treatment are shown in Supplement…