Plasma proprotein convertase subtilisin kexin type 9 levels are related to markers of cholesterol synthesis in familial combined hyperlipidemia

Brouwers, M.C.G.J.; Konrad, R.J.; van Himbergen, T.M.; Isaacs, A.; Otokozawa, S.; Troutt, J.S.; Schaefer, E.J.; van Greevenbroek, M.M.J.; Stalenhoef, A.F.H.; de Graaf, J.

doi:10.1016/j.numecd.2012.11.008

Cited by 24Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismLipid metabolism and disorders

Plasma proprotein convertase subtilisin kexin type 9 levels are related to markers of cholesterol synthesis in familial combined hyperlipidemia

Brouwers, M.C.G.J., Konrad, R.J., van Himbergen, T.M., Isaacs, A., Otokozawa, S., Troutt, J.S., Schaefer, E.J., van Greevenbroek, M.M.J. +2 more·2013·Nutrition, Metabolism and Cardiovascular Diseases

DOI 10.1016/j.numecd.2012.11.008

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Abstract

Background and aims Two recent independent studies showed that patients with familial combined hyperlipidemia (FCHL) have elevated plasma levels of proprotein convertase subtilisin kexin type 9 (PCSK9) and markers of cholesterol synthesis. Both PCSK9 expression and cholesterol synthesis are downstream effects of hepatic activation of sterol regulatory element binding protein 2 (SREBP2). The present study was conducted to study the relationship between plasma PCSK9 and markers of cholesterol synthesis in FCHL. Methods and results Markers of cholesterol synthesis (squalene, desmosterol, lathosterol), cholesterol absorption (campesterol, sitosterol, cholestanol) and PCSK9 were measured in plasma of FCHL patients (n = 103) and their normolipidemic relatives (NLR; n = 240). Plasma PCSK9, lathosterol and desmosterol levels were higher in FCHL patients than their NLR (p Conclusions The present study confirms the previously reported high and heritable PCSK9 levels in FCHL patients. Furthermore, we now show that high PCSK9 levels are, in part, explained by plasma lathosterol, suggesting that SREBP2 activation partly accounts for elevated PCSK9 levels in FCHL.

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Individuals with familial combined hyperlipidemia-1 have elevated levels of PCSK9, lathosterol, and desmosterol.
“Individuals with familial combined hyperlipidemia-1 have elevated levels of PCSK9 [102], lathosterol, and desmosterol [103], so individuals with low ApoB levels might have low lathosterol and desmosterol levels, as we detected in our subjects.”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [102]
Individuals with low ApoB levels might have low lathosterol and desmosterol levels, as we detected in our subjects.
“Individuals with familial combined hyperlipidemia-1 have elevated levels of PCSK9 [102], lathosterol, and desmosterol [103], so individuals with low ApoB levels might have low lathosterol and desmosterol levels, as we detected in our subjects.”
From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [102]

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Plasma proprotein convertase subtilisin kexin type 9 is a heritable trait of familial combined hyperlipidaemia
Brouwers, M. C. G. J., van Greevenbroek, M. M. J., Troutt, J. S., Freeman, A. B., Lu, A., Schaper, N. C., Konrad, R. J., & Stehouwer, C. D. A. (2011) · Clinical Science · doi:10.1042/cs20110129 · Cited by 15 · see citing works
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ASSOCIATION OF LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 (LP-PLA2) WITH PROPROTEIN CONVERTASE SUBTILISIN/KEXIN TYPE 9 (PCSK9) IN FAMILIAL HYPERCHOLESTEROLEMIA
Benimetskaya, K. S., Shramko, V. S., Stakhneva, E. M., Makarenkova, K. V., Shcherbakova, L. V., Ragino, Y. I., & Voevoda, M. I. (2019) · Ateroscleroz · doi:10.15372/ater20190102 · Cited by 1 · see citing works
Familial Combined Hyperlipidemia Is Associated With Alterations in the Cholesterol Synthesis Pathway
van Himbergen, T. M., Otokozawa, S., Matthan, N. R., Schaefer, E. J., Buchsbaum, A., Ai, M., van Tits, L. J. H., de Graaf, J., & Stalenhoef, A. F. H. (2010) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/atvbaha.109.196550 · Cited by 40 · see citing works
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Clinical and Population Studies Familial Combined Hyperlipidemia Is Associated With Alterations in the Cholesterol Synthesis Pathway
van Himbergen, T. M., Otokozawa, S., Matthan, N. R., Schaefer, E. J., Buchsbaum, A., Ai, M., Tits, L. J. H. V., Graaf, J. D., & Stalenhoef, A. F. H. (2016)
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Authors: Brouwers, M. C. G. J., Konrad, R. J., van Himbergen, T. M., Isaacs, A., Otokozawa, S., Troutt, J. S., Schaefer, E. J., van Greevenbroek, M. M. J., Stalenhoef, A. F. H., & de Graaf, J.
Affiliations: Maastricht University Medical Centre (NL)
Eli Lilly (United States) (US)
Erasmus MC (NL)
Tufts University (US)
Radboud University Medical Center (NL)
Corresponding author: Brouwers, M.C.G.J.
ORCID: Brouwers, M.C.G.J.
Konrad, R.J.
Isaacs, A.
Schaefer, E.J.
Venue: Nutrition, Metabolism and Cardiovascular Diseases
Publisher: Elsevier BV
Published: 2013-11
Volume: 23
Issue: 11
Pages: 1115-1121
ISSN: 0939-4753 (ISSN-L)
DOI: 10.1016/j.numecd.2012.11.008
OpenAlex: W2127272376
Cited by: 24
References: 25
Citations by year: 2025: 3 · 2021: 1 · 2019: 2 · 2018: 4 · 2017: 1 · 2016: 1 · 2015: 5 · 2014: 7
FWCI: 4.28
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Nutrition Metabolism and Cardiovascular Diseases (publishedVersion)
PubMed (publishedVersion)
Research Publications (Maastricht University) (publishedVersion)
Radboud Repository (Radboud University) (submittedVersion)
Research Publications (Maastricht University) (submittedVersion)
Topics: Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
Keywords: PCSK9, familial combined hyperlipidemia, cholesterol biosynthesis, lathosterol, desmosterol, SREBP2, heritability, genetic factors, cholesterol absorption, plasma sterols
MeSH terms: Proprotein Convertase 9, Adult, Cholesterol, Desmosterol, Family, Female, Humans, Hyperlipidemia, Familial Combined, Isomerism, Male, Middle Aged, Models, Biological, Netherlands, Regression Analysis, Serine Endopeptidases, Reproducibility of Results, Cohort Studies, Biomarkers, Up-Regulation, Multivariate Analysis, Proprotein Convertases

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Plasma proprotein convertase subtilisin kexin type 9 levels are related to markers of cholesterol synthesis in familial combined hyperlipidemia

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