Bianca E. Suur (Sweden)
Karolinska Institute Vascular SurgeryAuthor Of 1 Presentation
O008 - Proprotein Convertase Subtilisin/Kexin 6 is involved in lipid metabolism in liver and adipose tissue (ID 706)
Abstract
Background and Aims
PCSK6 is a protease strongly enriched in human liver however its function in liver has not been fully explored. Here, we aim to investigate the role of PCSK6 in lipid metabolism, and particularly in the context of atherosclerosis.
Methods
We used publically available datasets as well as biobanks to investigate the expression of PCSK6 in healthy and diseased tissues. In addition, we used Pcsk6-/- to investigate the effect of PCSK6 ablation.
Results
Genetic analyses of the PCSK6 locus identified a variant rs7181043 that was significantly associated with PCSK6 mRNA expression in healthy human adipose tissue, liver and in atherosclerotic plaques. The same variant was associated specifically with plaque fat content and atherosclerotic patient’s plasma LDL levels. In addition, PCSK6 mRNA expression in plaques was positively correlated with total plasma cholesterol and LDL levels in atherosclerotic patients. Further analyses using public scRNAseq data of healthy human livers, revealed that PCSK6 is expressed in hepatocytes and stellate cells. Microarray comparison of the livers from Pcsk6-/- mice and wild-type controls showed that VLDL particle assembly was one of the upregulated processes, in adipose tissue we found an increase in inflammatory infiltration and regulation of T cell mediated immunity. Preliminary in vivo studies showed that Pcsk6-/- mice have higher plasma cholesterol and LPL levels at baseline compared to controls, and lower levels of LDLR in their liver.
Conclusions
Our data suggests that PCSK6 is involved in cholesterol and metabolic control. Further experiments are warranted in order to understand the role of PCSK6 in lipid metabolism.
Presenter of 1 Presentation
O008 - Proprotein Convertase Subtilisin/Kexin 6 is involved in lipid metabolism in liver and adipose tissue (ID 706)
Abstract
Background and Aims
PCSK6 is a protease strongly enriched in human liver however its function in liver has not been fully explored. Here, we aim to investigate the role of PCSK6 in lipid metabolism, and particularly in the context of atherosclerosis.
Methods
We used publically available datasets as well as biobanks to investigate the expression of PCSK6 in healthy and diseased tissues. In addition, we used Pcsk6-/- to investigate the effect of PCSK6 ablation.
Results
Genetic analyses of the PCSK6 locus identified a variant rs7181043 that was significantly associated with PCSK6 mRNA expression in healthy human adipose tissue, liver and in atherosclerotic plaques. The same variant was associated specifically with plaque fat content and atherosclerotic patient’s plasma LDL levels. In addition, PCSK6 mRNA expression in plaques was positively correlated with total plasma cholesterol and LDL levels in atherosclerotic patients. Further analyses using public scRNAseq data of healthy human livers, revealed that PCSK6 is expressed in hepatocytes and stellate cells. Microarray comparison of the livers from Pcsk6-/- mice and wild-type controls showed that VLDL particle assembly was one of the upregulated processes, in adipose tissue we found an increase in inflammatory infiltration and regulation of T cell mediated immunity. Preliminary in vivo studies showed that Pcsk6-/- mice have higher plasma cholesterol and LPL levels at baseline compared to controls, and lower levels of LDLR in their liver.
Conclusions
Our data suggests that PCSK6 is involved in cholesterol and metabolic control. Further experiments are warranted in order to understand the role of PCSK6 in lipid metabolism.