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Lipoprotein profile...
Lipoprotein profiles in human heterozygote carriers of a functional mutation P297S in scavenger receptor class B1.
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Ljunggren, Stefan A (author)
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Levels, Johannes H M (author)
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Hovingh, Kees (author)
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Holleboom, Adriaan G (author)
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Vergeer, Menno (author)
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Argyri, Letta (author)
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Gkolfinopoulou, Christina (author)
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Chroni, Angeliki (author)
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Sierts, Jeroen A (author)
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Kastelein, John J (author)
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Kuivenhoven, Jan Albert (author)
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Lindahl, Mats (author)
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Karlsson, Helen (author)
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- Elsevier 2015
- 2015
- English.
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In: Biochimica et Biophysica Acta. - 0006-3002. ; 1851:12, 1587-1595
Abstract
Subject headings
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- The scavenger receptor class B type 1 (SR-B1) is an important HDL receptor involved in cholesterol uptake and efflux, but its physiological role in human lipoprotein metabolism is not fully understood. Heterozygous carriers of the SR-B1 P297S mutation are characterized by increased HDL cholesterol levels, impaired cholesterol efflux from macrophages and attenuated adrenal function. Here, the composition and function of lipoproteins were studied in SR-B1 P297S heterozygotes. Lipoproteins from six SR-B1 P297S carriers and six family controls were investigated. HDL and LDL/VLDL were isolated by ultracentrifugation and proteins were separated by two-dimensional gel electrophoresis and identified by mass spectrometry. HDL antioxidant properties, paraoxonase 1 activities, apoA-I methionine oxidations and HDL cholesterol efflux capacity were assessed. Multivariate modeling separated carriers from controls based on lipoprotein composition. Protein analyses showed a significant enrichment of apoE in LDL/VLDL and of apoL-1 in HDL from heterozygotes compared to controls. The relative distribution of plasma apoE was increased in LDL and in lipid-free form. There were no significant differences in paraoxonase 1 activities, HDL antioxidant properties or HDL cholesterol efflux capacity but heterozygotes showed a significant increase of oxidized methionines in apoA-I. The SR-B1 P297S mutation affects both HDL and LDL/VLDL protein compositions. The increase of apoE in carriers suggests a compensatory mechanism for attenuated SR-B1 mediated cholesterol uptake by HDL. Increased methionine oxidation may affect HDL function by reducing apoA-I binding to its targets. The results illustrate the complexity of lipoprotein metabolism that has to be taken into account in future therapeutic strategies aiming at targeting SR-B1.
Subject headings
- Natural Sciences (hsv)
- Biological Sciences (hsv)
- Biochemistry and Molecular Biology (hsv)
- Naturvetenskap (hsv)
- Biologiska vetenskaper (hsv)
- Biokemi och molekylärbiologi (hsv)
Keyword
- ApoE; ApoL-1; HDL; LDL/VLDL; P297S; SR-B1
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- By the author/editor
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Ljunggren, Stefa ...
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Levels, Johannes ...
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Hovingh, Kees
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Holleboom, Adria ...
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Vergeer, Menno
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Argyri, Letta
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show more...
-
Gkolfinopoulou, ...
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Chroni, Angeliki
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Sierts, Jeroen A
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Kastelein, John ...
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Kuivenhoven, Jan ...
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Lindahl, Mats
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Karlsson, Helen
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show less...
- By the university
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