Proprotein convertase subtilisin kexin type 9 (PCSK9) belongs to the proprotein convertase family. Several studies have demonstrated its involvement in the regulation of low-density lipoprotein (LDL) cholesterol levels by inducing the degradation of the LDL receptor (LDLR). However, experimental, epidemiologic, and pharmacologic data provide important evidence on the role of PCSK9 also on high-density lipoproteins (HDLs). In mice, PCSK9 regulates the HDL cholesterol (HDL-C) levels by the degradation of hepatic LDLR, thus driving the uptake of apolipoprotein (Apo)E-containing HDLs. Several epidemiologic and genetic studies reported positive relationship between PCSK9 and HDL-C levels, likely by reducing the uptake of the ApoE-containing HDL particles. PCSK9 enhances also the degradation of LDLR's closest family members, ApoE receptor 2, very low-density lipoprotein receptor, and LDLR-related protein 1. This feature provides a molecular mechanism by which PCSK9 may affect HDL metabolism. Experimental studies demonstrated that PCSK9 directly interacts with HDL by modulating PCSK9 self-assembly and its binding to the LDLR. Finally, the inhibition of PCSK9 by means of monoclonal antibodies directed to PCSK9 (ie, evolocumab and alirocumab) determines an increase of HDL-C fraction by 7% and 4.2%, respectively. Taken together, the understanding of the role of PCSK9 on HDL metabolism needs to be elucidated with a particular focus on the effect of PCSK9 on HDL-mediated reverse cholesterol transport.

Proprotein convertase subtilisin kexin type 9 and high-density lipoprotein metabolism : experimental animal models and clinical evidence / N. Ferri, A. Corsini, C. Macchi, P. Magni, M. Ruscica. - In: TRANSLATIONAL RESEARCH. - ISSN 1931-5244. - 173(2016 Jul), pp. 19-29. [10.1016/j.trsl.2015.10.004]

Proprotein convertase subtilisin kexin type 9 and high-density lipoprotein metabolism : experimental animal models and clinical evidence

N. Ferri
Primo
;
A. Corsini
Secondo
;
C. Macchi;P. Magni
Penultimo
;
M. Ruscica
Ultimo
2016

Abstract

Proprotein convertase subtilisin kexin type 9 (PCSK9) belongs to the proprotein convertase family. Several studies have demonstrated its involvement in the regulation of low-density lipoprotein (LDL) cholesterol levels by inducing the degradation of the LDL receptor (LDLR). However, experimental, epidemiologic, and pharmacologic data provide important evidence on the role of PCSK9 also on high-density lipoproteins (HDLs). In mice, PCSK9 regulates the HDL cholesterol (HDL-C) levels by the degradation of hepatic LDLR, thus driving the uptake of apolipoprotein (Apo)E-containing HDLs. Several epidemiologic and genetic studies reported positive relationship between PCSK9 and HDL-C levels, likely by reducing the uptake of the ApoE-containing HDL particles. PCSK9 enhances also the degradation of LDLR's closest family members, ApoE receptor 2, very low-density lipoprotein receptor, and LDLR-related protein 1. This feature provides a molecular mechanism by which PCSK9 may affect HDL metabolism. Experimental studies demonstrated that PCSK9 directly interacts with HDL by modulating PCSK9 self-assembly and its binding to the LDLR. Finally, the inhibition of PCSK9 by means of monoclonal antibodies directed to PCSK9 (ie, evolocumab and alirocumab) determines an increase of HDL-C fraction by 7% and 4.2%, respectively. Taken together, the understanding of the role of PCSK9 on HDL metabolism needs to be elucidated with a particular focus on the effect of PCSK9 on HDL-mediated reverse cholesterol transport.
proprotein convertase Subtilisin/Kexin 9
Settore MED/04 - Patologia Generale
Settore MED/05 - Patologia Clinica
Settore BIO/14 - Farmacologia
Settore MED/13 - Endocrinologia
Settore MED/46 - Scienze Tecniche di Medicina di Laboratorio
lug-2016
20-ott-2015
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/334193
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