by Saik Olga | Klimontov Vadim | RICEL – Branch of IC&G SB RAS | RICEL – Branch of IC&G SB RAS<\/p>\n
<\/p>\n
Background<\/strong>: High glucose variability (GV) is recognized as a contributor for diabetic
\nmicrovascular and macrovascular complications, including diabetic retinopathy, chronic
\nkidney disease, diabetic neuropathy, and macrovascular disease. The results of numerous
\nstudies have pointed to the role of endothelial dysfunction in the development of these
\ncomplications.
\nThe aim<\/strong>: to identify genes linking GV with endothelial dysfunction in diabetes.
\nMethods<\/strong>: The gene networks reconstruction and analysis were performed by the
\nANDSystem (www-bionet.sscc.ru\/and\/cell\/).
\nResults<\/strong>: Sixty genes related to GV and endothelial dysfunction were found. The probability
\nof observing so many common genes for random reasons is very small (p-value<10-47). The\nidentified genes\/proteins are involved in the activation, apoptosis, development,\ndifferentiation, migration, morphogenesis and proliferation of endothelial cells. It was found\nthat in the GV gene network many genes associated with endothelial dysfunction have\nrelatively high values of betweenness centrality. The average of betweenness centrality\nvalues for the common 60 genes involved in endothelial dysfunction and GV was 536, while\nfor all GV genes it was only 270. The difference of the betweenness centrality values for\nthese two gene sets is statistically significant (P-value=10-5, Mann-Whitney U test). All the\ntop ten genes with highest betweenness centrality values in the GV gene network (INS, IL6,\nTP53, FOXO1, LEP, MAPK14, TNF, IL1B, IGF1, and VEGFA) were also involved in the\nendothelial dysfunction.\nConclusions<\/strong>: Discovering the key genes involved both in the GV and endothelial
\ndysfunction could shed light on understanding of the pathogenesis of diabetes complications
\nand could support the future drug development.
\nThis work was supported by the grant of Russian Science Foundation
\n(20-15-00057).<\/p>\nBGRS2022-GV and endothelial dysfunction_new