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Review
. 2020 May;46(3):367-380.
doi: 10.1002/biof.1619. Epub 2020 Jan 30.

Beyond cholesterol metabolism: The pleiotropic effects of proprotein convertase subtilisin/kexin type 9 (PCSK9). Genetics, mutations, expression, and perspective for long-term inhibition

Arturo Cesaro  1   2 , Vanessa Bianconi  3 , Felice Gragnano  1   2 , Elisabetta Moscarella  1   2 , Fabio Fimiani  1   2 , Emanuele Monda  2   4 , Olga Scudiero  5   6 , Giuseppe Limongelli  2   4 , Matteo Pirro  3 , Paolo Calabrò  1   2
Affiliations
Review

Beyond cholesterol metabolism: The pleiotropic effects of proprotein convertase subtilisin/kexin type 9 (PCSK9). Genetics, mutations, expression, and perspective for long-term inhibition

Arturo Cesaro et al. Biofactors. 2020 May.

Abstract

Proprotein convertase subtilisin/kexin type 9 (PCSK9) has a crucial role in lipid metabolism, particularly due to its function in low-density lipoprotein receptor degradation. Gain-of-function genetic mutations of PCSK9 result in autosomal dominant familial hypercholesterolemia, characterized by high levels of low-density lipoprotein cholesterol (LDL-C) and clinical signs of early atherosclerosis. In recent years, PCSK9 has become an important therapeutic target for cholesterol-lowering therapy. Particularly, its inhibition with monoclonal antibodies has shown excellent efficacy in decreasing LDL-C and reducing cardiovascular events. However, PCSK9, first identified in the brain, seems to be a ubiquitous protein with different tissue-specific functions also independent of cholesterol metabolism. Accordingly, it appears to be involved in the immune response, haemostasis, glucose metabolism, neuronal survival, and several other biological functions. This review provides a comprehensive overview of the genetics, biochemical structure, expression, and function of PCSK9 and discusses the potential implications of its long-term pharmacological inhibition.

Keywords: PCSK9; dyslipidemia; familial hypercholesterolemia; low-density lipoprotein; pleiotropic effects.

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References

REFERENCES

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