Biology of proprotein convertase subtilisin kexin 9: Beyond low-density lipoprotein cholesterol lowering
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© 2016 The Author. Proprotein convertase subtilisin kexin 9 (PCSK9) is a key regulator of low-density lipoprotein receptor levels and LDL-cholesterol levels. Loss-of-function mutations in PCSK9 gene are associated with hypocholesterolaemia and protection against cardiovascular disease, identifying PCSK9 inhibition as a valid therapeutic approach to manage hypercholesterolaemia and related diseases. Although PCSK9 is expressed mainly in the liver, it is present also in other tissues and organs with specific functions, raising the question of whether a pharmacological inhibition of PCSK9 to treat hypercholesterolaemia and associated cardiovascular diseases might be helpful or deleterious in non-hepatic tissues. For example, PCSK9 is expressed in the vascular wall, in the kidneys, and in the brain, where it was proposed to play a role in development, neurocognitive process, and neuronal apoptosis. A link between PCSK9 and immunity was also proposed as both sepsis and viral infections are differentially affected in the presence or absence of PCSK9. Despite the increasing number of observations, the debate on the exact roles of PCSK9 in extrahepatic tissues is still ongoing, and as very effective drugs that inhibit PCSK9 have become available to the clinician, a better understanding of the biological roles of PCSK9 is warranted.
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Norata, Giuseppe; Tibolla, G.; Catapano, A. (2014)Hypercholesterolemia, is a prominent risk factor for cardiovascular disease (CVD). Undestanding of the biochemical mechanisms that regulate the expression of the low density lipoproteins receptor (LDLR) and the hepatic ...
Proprotein convertase subtilisin/kexin type 9 (PCSK9): From structure-function relation to therapeutic inhibitionTibolla, G.; Norata, Giuseppe; Artali, R.; Meneghetti, F.; Catapano, A. (2011)Aims: This short review aims at summarizing the current information on Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) structure and function focusing also on the therapeutic possibilities based on the inhibition ...
Baragetti, A.; Balzarotti, G.; Grigore, L.; Pellegatta, F.; Guerrini, U.; Pisano, G.; Fracanzani, A.; Fargion, S.; Norata, Giuseppe; Catapano, A. (2017)Â© 2017, Â© The European Society of Cardiology 2017. Background: Proprotein convertase subtilisin kexin type 9 (PCSK9) regulates low-density lipoprotein and very low-density lipoprotein receptor expression in several ...