High Concentration of Low-Density Lipoprotein Results in Disturbances in Mitochondrial Transcription and Functionality in Endothelial Cells.

ABSTRACT: Concentrations of low-density lipoprotein (LDL) above 0.8 mg/ml have been associated with increased risk for cardiovascular diseases and impaired endothelial functionality. Here, we demonstrate that high concentrations of LDL (1 mg/ml) decreased NOS3 protein and RNA levels in primary human endothelial cells. In addition, RNA sequencing data, in particular splice site usage analysis, showed a shift in NOS3 exon-exon junction reads towards those specifically assigned to nonfunctional transcript isoforms further diminishing the functional NOS3 levels. The reduction in NOS3 was accompanied by decreased migratory capacity, which depends on intact mitochondria and ATP formation. In line with these findings, we also observed a reduced ATP content. While mitochondrial mass was unaffected by high L

SUBMITTER: Gonnissen S 

PROVIDER: S-EPMC6590621 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature