Monocytic microRNA profile associated with coronary collateral artery function in chronic total occlusion patients.
Nazanin HakimzadehJoëlle EliasGilbert W M WijntjensRuud TheunissenAngela van WeertMartijn W SmuldersNynke van den AkkerPerry D MoerlandHein J VerberneLoes P HoebersJose P S HenriquesAnja M van der LaanMustafa IlhanMark PostSebastiaan C A M BekkersJan J PiekPublished in: Scientific reports (2017)
An expansive collateral artery network is correlated with improved survival in case of adverse cardiac episodes. We aimed to identify cellular microRNAs (miRNA; miR) important for collateral artery growth. Chronic total occlusion (CTO) patients (n = 26) were dichotomized using pressure-derived collateral flow index (CFIp) measurements; high collateral capacity (CFIp > 0.39; n = 14) and low collateral (CFIp < 0.39; n = 12) capacity. MiRNA profiling via next generation sequencing from various monocyte phenotypes (freshly isolated monocytes, monocytes cultured without stimulant, or stimulation with lipopolysaccharide, interleukin 4, transforming growth factor beta-1, or interferon gamma) revealed significantly different miRNA expression patterns between high versus low collateral capacity patients. Validation by real-time polymerase chain reaction demonstrated significantly decreased expression of miR339-5p in all stimulated monocyte phenotypes of low collateral capacity patients. MiR339-5p showed significant correlation with CFIp values in stimulated monocytes. Ingenuity pathway analysis of predicted gene targets of miR339-5p and differential gene expression data from high versus low CFIp patients (n = 20), revealed significant association with STAT3 pathway, and also suggested a possible regulatory role for this signaling pathway. These results identify a novel association between miR339-5p and coronary collateral function. Future work examining modulation of miR339-5p and downstream effects on the STAT3 pathway and subsequent collateral vessel growth are warranted.
Keyphrases
- end stage renal disease
- gene expression
- newly diagnosed
- chronic kidney disease
- ejection fraction
- signaling pathway
- heart failure
- transforming growth factor
- cell proliferation
- epithelial mesenchymal transition
- coronary artery
- coronary artery disease
- endothelial cells
- immune response
- left ventricular
- single cell
- peripheral blood
- toll like receptor
- inflammatory response
- artificial intelligence
- transcatheter aortic valve replacement
- patient reported
- circulating tumor cells