The DOI matches its Crossref record.
Associations Between Soluble LDLR and Lipoproteins in a White Cohort and the Effect of PCSK9 Loss-of-Function
Abstract
Context Elevated circulating cholesterol-rich low-density lipoprotein (LDL) particles increase coronary artery disease risk. Cell-surface hepatic LDL receptors (LDLRs) clear 70% of these particles from circulation. The ectodomain of LDLR is shed into circulation, preventing it from removing LDL particles. The role that LDLR ectodomain shedding plays as a regulatory mechanism is unknown. Objective We describe LDLR shedding via the relationships between circulating soluble LDLRs (sLDLRs) and serum lipoproteins, serum proprotein convertase subtilin/kexin type 9 (PCSK9; a negative regulator of LDLR), and clinical parameters in a white Canadian population. Design Population-based, cross-sectional study. Settings Clinical Research Center, The Ottawa Hospital, and Faculty of Medicine, University of Ottawa. Participants Two hundred seventy-three white Canadians. Intervention None. Main outcome measures sLDLR measured by ELISA; serum lipids and PCSK9, PCSK9 genotypes, and clinical parameters from previous analyses. Results sLDLRs correlated strongly with triglycerides (TG; r = 0.624, P 50th or LDL cholesterol >75th percentiles. Conclusions Serum sLDLR levels correlate with several lipoprotein parameters, especially TG, and the presence of PCSK9 loss-of-function variants alters sLDLR levels and correlations, except for TG. Ectodomain LDLR shedding has a role in LDL metabolism, distinct from PCSK9, with interplay between these two pathways that regulate cell-surface LDLRs. Findings sugg…
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Two independent studies revealed a mild but significant correlation between serum concentrations of sLDLR and LDL-C in healthy adult Japanese and Canadian white populations.
“Consistently, two independent studies revealed a mild but significant correlation between serum concentrations of sLDLR and LDL-C in healthy adult Japanese and Canadian white population11,14.”
From Membrane type 1 matrix metalloproteinase promotes LDL receptor shedding and accelerates the development of atherosclerosis (2021) · cites this paper as [14]
Serum levels of sLDLR are positively correlated with plasma LDL-C levels.
“Serum levels of sLDLR are positively correlated with plasma LDL-C levels11,14.”
From Membrane type 1 matrix metalloproteinase promotes LDL receptor shedding and accelerates the development of atherosclerosis (2021) · cites this paper as [14]
Plasma levels of soluble LDLR (sLDLR) are positively correlated with circulating LDL-C levels.
“It has been reported that plasma levels of sLDLR are positively correlated to circulating LDL-C levels (15–17).”
From Identification of amino acid residues in the MT-loop of MT1-MMP critical for its ability to cleave low-density lipoprotein receptor (2022) · cites this paper as [17]
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Cited by
Sorted by citations
Alabi, A., Xia, X.-D., Gu, H.-M., Wang, F., Deng, S.-J., Yang, N., Adijiang, A., Douglas, D. N., Kneteman, N. M., Xue, Y., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-22167-3 · Cited by 63
Roubtsova, A., Garçon, D., Lacoste, S., Chamberland, A., Marcinkiewicz, J., Métivier, R., Sotin, T., Paquette, M., Bernard, S., Cariou, B., et al. (2022) · Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids · doi:10.1016/j.bbalip.2022.159217 · Cited by 22
Wang, M., Alabi, A., Gu, H.-M., Gill, G., Zhang, Z., Jarad, S., Xia, X.-D., Shen, Y., Wang, G.-Q., & Zhang, D.-W. (2022) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2022.917238 · Cited by 13
Metadata
- Authors
- Mayne, J., Ooi, T. C., Tepliakova, L., Seebun, D., Walker, K., Mohottalage, D., Ning, Z., Abujrad, H., Mbikay, M., Wassef, H., Chrétien, M., & Figeys, D.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2018-06-21
- Volume
- 103
- Issue
- 9
- Pages
- 3486-3495
- ISSN
- 0021-972X
- 1945-7197
- Cited by
- 24
- References
- 0
- Language
- en
- Funders
- Heart and Stroke Foundation of Canada (G-16-00014693, NA-7278)
- La Foundation J-Louis Lévesque
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