Dosenko V. The role of allelic polymorphism of endothelial NO-synthase and proteasome genes in pathogenesis of cardio-vascular diseases: molecular and genetic aspects

The work is devoted to investigation of the role of promoter (Т-786?С), exon 7 (G894/T) and intron 4 (4b/4a) of endothelial NO-synthase (eNOS) and LMP2 (Arg60 His) and LMP7 (Lys145 Gln) allelic polymorphism in pathogenesis of cardio-vascular disease. Obtained data show that С/С promoter variant of eNOS is in 2.7-fold more frequent at patients with acute coronary syndrome, than in practically healthy subjects. Level of eNOS gene expression is on 35% less at the C/C genotype, than at the T/T variant of promoter. Activity of NO production in platelets of people with the C/C variant of promoter is in 2.1 times less than it is at the T/T genotype. It specifies to the functional value of this allelic polymorphism. Distribution of different allelic variants of LMP2 and LMP7 genes does not differ in patients with cardio-vascular disease and in practically healthy subjects. With the use of developed method it was shown that mRNA of different NOS іsoform hydrolyzed by 26S proteasome, which indicates the participation of proteasomal proteolysis in regulation of the eNOS activity both on posttranscriptional and posttranslational levels. In vitro and cardiomyocyte culture experiments was shown that the cardioprotective mechanisms of quercetin are related to influence on proteasomal proteolysis.