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Structure and Function of Proprotein Convertase Subtilisin/kexin Type 9 (PCSK9) in Hyperlipidemia and Atherosclerosis

Author(s):

Xinjie Lu*   Pages 1 - 12 ( 12 )

Abstract:


Background: One of the important factors in low-density lipoprotein (LDL) metabolism is the LDL receptor (LDLR) by its capacity to bind and subsequently clear cholesterol derived from LDL (LDL-C) in the circulation. Proprotein convertase subtilisin-like kexin type 9 (PCSK9) is a newly discovered serine protease that destroys LDLR in the liver and thereby controls the levels of LDL in plasma. Inhibition of PCSK9-mediated degradation of LDLR has, therefore, become a novel target for lipid-lowering therapy.

Method: We review the current understanding of the structure and function of PCSK9 as well as its implications for the treatment of hyperlipidemia and atherosclerosis.

Results: New treatments such as monoclonal antibodies against PCSK9 may be useful agents to lower plasma levels of LDL and hence prevent atherosclerosis.

Conclusions: PCSK9's mechanism of action is not yet fully clarified. However, treatments that target PCSK9 have shown striking early efficacy and promise to improve the lives of countless patients with hyperlipidemia and atherosclerosis.

Keywords:

Proprotein convertase subtilisin/kexin type 9 (PCSK9), low-density lipoprotein cholesterol (LDL-C), LDL receptor (LDLR), atherosclerosis, monoclonal antibody, vaccine.

Affiliation:

The Mary and Garry Weston Molecular Immunology Laboratory, Thrombosis Research Institute, London, SW3 6LR



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