Plasma PCSK9 level affects passively LAMP-2 expression; an evidence of transcription network

Abstract

Free cholesterol accumulation in lysosomes is related to highly glycosylated membrane-protein functions, endogenous cholesterol synthesis and, LDL influx. The LAMP-1 and LAMP-2 are two lysosome proteins involved in cholesterol transport. The study aim was to investigate the associations between LAMP-2 expression level, LAMP-2/LAMP-1 expression ratio, blood PCSK9 protein and LDL-C values. One hundred twenty six healthy subjects were selected during a medical interview. The biochemical parameters were measured using routine laboratory techniques. The plasma PCSK9 level was identified by ELISA method. The LAMP-1/LAMP-2 expression levels were estimated by Real time qPCR technique. The PCSK9 and LAMP-2 expression networks were designed with Cytoscape software and, were enriched using transcription factor databases. Linear correlations were observed between PCSK9 and LDL-C levels (r=0.34; p=0.002) and, TC/HDL-C ratio (r=0.35; p=0.001). The LAMP-2 expression level and LAMP-2/LAMP-1 expression ratio were inversely related to LDL-C values (p=0.02). The transcription factors were compartmented on the merged network and were strictly controlled the PCSK9 expression. The results suggested that the decreased LDL influx due to the increase of plasma PCSK9 level attenuates the LAMP-2 gene expression level. Furthermore, the merged network supported our findings that the LAMP-2 expression is not in relation to transcription factors involved with PCSK9 expression.