2019
DOI: 10.1177/0004563219864379
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PCSK9: from molecular biology to clinical applications

Abstract: Proprotein convertase subtilisin kexin 9 (PCSK9) is a serine protease with a key role in regulating plasma low-density lipoprotein (LDL) concentration. Since its discovery via parallel molecular biology and clinical genetics studies in 2003, work to characterize PCSK9 has shed new light on the life-cycle of the low-density lipoprotein receptor and the molecular basis of familial hypercholesterolaemia. These discoveries have also led to the advent of the PCSK9 inhibitors, a new generation of low-density lipopro… Show more

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Cited by 7 publications
(6 citation statements)
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References 134 publications
(222 reference statements)
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“…PCSK9 has generally been measured by ELISA immunoassay, while the concentrations varied in a wide range (40-800 ng/ml) among different ELISA techniques (64). Studies making the head-to-head comparison of the methods to investigate the differences are scarce (64). Hence, the wide variability of results would substantially limit the utility of PCSK9 measurement in clinical practice.…”
Section: Discussionmentioning
confidence: 99%
“…PCSK9 has generally been measured by ELISA immunoassay, while the concentrations varied in a wide range (40-800 ng/ml) among different ELISA techniques (64). Studies making the head-to-head comparison of the methods to investigate the differences are scarce (64). Hence, the wide variability of results would substantially limit the utility of PCSK9 measurement in clinical practice.…”
Section: Discussionmentioning
confidence: 99%
“…Lastly, the C-terminal domain consisting of the three modules is attached to the catalytic domain [38]. While PCSK9 is a serine protease, the degradation of LDLR does not require proteolytic activity of PCSK9, only the ability of PCSK9 to chaperone LDLR towards lysosomes [40]. PCSK9 is synthesised in the endoplasmic reticulum (ER) with the help of transcription factors sterol-response element binding protein (SREBP-1/2), hepatocyte nuclear factor 1α (HNF1α), forkhead box O3 (FoxO3), Peroxisome proliferator-activated receptor α and γ (PPARα and PPARγ).…”
Section: Pcsk9 Biologymentioning
confidence: 99%
“…The review article recently written by Malo et al. 1 is a thorough overview of the currently available knowledge concerning proprotein convertase subtilisin/kexin type 9 (PCSK9), including descriptions of its molecular, physicochemical and clinical aspects. Research on PCSK9 has promoted our understanding of low-density lipoprotein (LDL) regulation, and reduced cardiovascular disease (CVD) event rates have been observed in studies using PCSK9 inhibitors.…”
mentioning
confidence: 99%
“…Research on PCSK9 has promoted our understanding of low-density lipoprotein (LDL) regulation, and reduced cardiovascular disease (CVD) event rates have been observed in studies using PCSK9 inhibitors. 1 Malo et al. noted that important questions remain regarding PCSK9, without specifying its relation to lipoprotein(a) (Lp(a)).…”
mentioning
confidence: 99%
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