Abstract
Proprotein convertase subtilisin-kexin 9 (PCSK9) appears to be involved in multiple processes. A ProtoArray Human Protein Microarray was used to identify proteins interacting with biotinylated PCSK9. Fifteen novel proteins interacting with PCSK9 were identified using this technique. Only two of these proteins, sterol carrier protein 2 and hepatoma-derived growth factor, related protein 3, have known functions. The identification of proteins that could affect the expression/function of PCSK9 is of great interest due to potential implications in personalized medicine for hypercholesterolemic patients.
Highlights
Hypercholesterolemia, which is a major issue in the United States due to the number of patients that suffer this disease, is well-known to improve with diet, exercise, and in the majority of the case, with the use of anti-hypercholesterolemic treatments [1]
Centrifugation was performed at 1000 × g for 2 minutes, and the resulting flow-through that contained the rPCSK9 protein in PBS was used in the step
Human rPCSK9 was first biotinylated as indicated in Materials and Methods
Summary
Hypercholesterolemia, which is a major issue in the United States due to the number of patients that suffer this disease, is well-known to improve with diet, exercise, and in the majority of the case, with the use of anti-hypercholesterolemic treatments [1]. A gene that has been identified as responsible for statin resistance is proprotein convertase subtilisin/kexin 9 (PCSK9) [4]. Another group of patients (10–25%) suffer from statin intolerance limiting the use of these drugs in these patients [2,3]. Serum levels of PCSK9 are associated positively with LDL levels in FH patients and appear to contribute to the phenotypic severity of the FH disorder [11,12] Both gain-of-function (GOF) and loss-of-function (LOF) mutations in the PCSK9 gene have been reported. The LOF mutations, on the other hand, result in hypocholesterolemia and protection against cardiovascular diseases [15,16]
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