The enigma of soluble LDLR: could inflammation be the key?

doi:10.1186/s12944-020-1199-9

. 2020 Feb 3;19(1):17.

doi: 10.1186/s12944-020-1199-9.

The enigma of soluble LDLR: could inflammation be the key?

Majambu Mbikay^{1

2}, Janice Mayne³, Michel Chrétien^{4

5

3}

Affiliations

¹ Functional Endoproteolysis Laboratory, Clinical Research Institute of Montreal, 110 avenue des Pins Ouest, Montréal, Québec, H2W 1R7, Canada. majambu.mbikay@ircm.qc.ca.
² Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. majambu.mbikay@ircm.qc.ca.
³ Department of Biochemistry, Microbiology and Immunology, University of Ottawa Faculty of Medicine, Ottawa, ON, Canada.
⁴ Functional Endoproteolysis Laboratory, Clinical Research Institute of Montreal, 110 avenue des Pins Ouest, Montréal, Québec, H2W 1R7, Canada.
⁵ Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

PMID: 32014013
PMCID: PMC6998292
DOI: 10.1186/s12944-020-1199-9

The enigma of soluble LDLR: could inflammation be the key?

Majambu Mbikay et al. Lipids Health Dis. 2020.

. 2020 Feb 3;19(1):17.

doi: 10.1186/s12944-020-1199-9.

Authors

Majambu Mbikay^{1

2}, Janice Mayne³, Michel Chrétien^{4

5

3}

Affiliations

¹ Functional Endoproteolysis Laboratory, Clinical Research Institute of Montreal, 110 avenue des Pins Ouest, Montréal, Québec, H2W 1R7, Canada. majambu.mbikay@ircm.qc.ca.
² Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada. majambu.mbikay@ircm.qc.ca.
³ Department of Biochemistry, Microbiology and Immunology, University of Ottawa Faculty of Medicine, Ottawa, ON, Canada.
⁴ Functional Endoproteolysis Laboratory, Clinical Research Institute of Montreal, 110 avenue des Pins Ouest, Montréal, Québec, H2W 1R7, Canada.
⁵ Chronic Disease Program, Ottawa Hospital Research Institute, Ottawa, ON, Canada.

PMID: 32014013
PMCID: PMC6998292
DOI: 10.1186/s12944-020-1199-9

Abstract

Soluble low-density lipoprotein receptor (sLDLR) is the circulating ectodomain of transmembrane LDLR. Its blood level strongly correlates with that of triglycerides (TG). This correlation has eluded satisfactory explanation. Hypertriglyceridemia and shedding of the ectodomain of many transmembrane receptors often accompany inflammatory states. The shedding mostly occurs through cleavage by a disintegrin-and-metalloproteinase-17 (ADAM-17), an enzyme activated by inflammation. It reduces the cellular uptake of TG-loaded lipoproteins, causing their accumulation in circulation; hence the correlation between plasma sLDLR and TG. Soluble LDLR could become a new surrogate marker of inflammation.

Keywords: ADAM-17; Ectodomain shedding; Inflammation; Soluble LDLR.

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Conflict of interest statement

The authors declare that they have no competing interests.

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References

1. Fischer DG, Tal N, Novick D, Barak S, Rubinstein M. An antiviral soluble form of the LDL receptor induced by interferon. Science. 1993;262:250–253. doi: 10.1126/science.8211145. - DOI - PubMed
1. Fischer DG, Novick D, Cohen B, Rubinstein M. Isolation and characterization of a soluble form of the LDL receptor, an interferon-induced antiviral protein. Proc Soc Exp Biol Med. 1994;206:228–232. doi: 10.3181/00379727-206-43749. - DOI - PubMed
1. Shimohiro H, Taniguchi S, Koda M, Sakai C, Yamada S. Association between serum soluble low-density lipoprotein receptor levels and metabolic factors in healthy Japanese individuals. J Clin Lab Anal. 2015;29:52–56. doi: 10.1002/jcla.21727. - DOI - PMC - PubMed
1. Mayne J, Ooi TC, Tepliakova L, Seebun D, Walker K, Mohottalage D, Ning Z, Abujrad H, Mbikay M, Wassef H, et al. Associations between soluble LDLR and lipoproteins in a white cohort and the effect of PCSK9 loss-of-function. J Clin Endocrinol Metab. 2018;103:3486–3495. doi: 10.1210/jc.2018-00777. - DOI - PubMed
1. Girona J, Rodriguez-Borjabad C, Ibarretxe D, Heras M, Amigo N, Feliu A, Masana L, Plana N, Group D Plasma inducible degrader of the LDLR, soluble low-density lipoprotein receptor, and proprotein convertase subtilisin/kexin type 9 levels as potential biomarkers of familial hypercholesterolemia in children. J Clin Lipidol. 2018;12:211–218. doi: 10.1016/j.jacl.2017.10.003. - DOI - PubMed

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[1] Fischer DG, Tal N, Novick D, Barak S, Rubinstein M. An antiviral soluble form of the LDL receptor induced by interferon. Science. 1993;262:250–253. doi: 10.1126/science.8211145. - DOI - PubMed

[2] Fischer DG, Tal N, Novick D, Barak S, Rubinstein M. An antiviral soluble form of the LDL receptor induced by interferon. Science. 1993;262:250–253. doi: 10.1126/science.8211145. - DOI - PubMed

[3] Fischer DG, Novick D, Cohen B, Rubinstein M. Isolation and characterization of a soluble form of the LDL receptor, an interferon-induced antiviral protein. Proc Soc Exp Biol Med. 1994;206:228–232. doi: 10.3181/00379727-206-43749. - DOI - PubMed

[4] Fischer DG, Novick D, Cohen B, Rubinstein M. Isolation and characterization of a soluble form of the LDL receptor, an interferon-induced antiviral protein. Proc Soc Exp Biol Med. 1994;206:228–232. doi: 10.3181/00379727-206-43749. - DOI - PubMed

[5] Shimohiro H, Taniguchi S, Koda M, Sakai C, Yamada S. Association between serum soluble low-density lipoprotein receptor levels and metabolic factors in healthy Japanese individuals. J Clin Lab Anal. 2015;29:52–56. doi: 10.1002/jcla.21727. - DOI - PMC - PubMed

[6] Shimohiro H, Taniguchi S, Koda M, Sakai C, Yamada S. Association between serum soluble low-density lipoprotein receptor levels and metabolic factors in healthy Japanese individuals. J Clin Lab Anal. 2015;29:52–56. doi: 10.1002/jcla.21727. - DOI - PMC - PubMed

[7] Mayne J, Ooi TC, Tepliakova L, Seebun D, Walker K, Mohottalage D, Ning Z, Abujrad H, Mbikay M, Wassef H, et al. Associations between soluble LDLR and lipoproteins in a white cohort and the effect of PCSK9 loss-of-function. J Clin Endocrinol Metab. 2018;103:3486–3495. doi: 10.1210/jc.2018-00777. - DOI - PubMed

[8] Mayne J, Ooi TC, Tepliakova L, Seebun D, Walker K, Mohottalage D, Ning Z, Abujrad H, Mbikay M, Wassef H, et al. Associations between soluble LDLR and lipoproteins in a white cohort and the effect of PCSK9 loss-of-function. J Clin Endocrinol Metab. 2018;103:3486–3495. doi: 10.1210/jc.2018-00777. - DOI - PubMed

[9] Girona J, Rodriguez-Borjabad C, Ibarretxe D, Heras M, Amigo N, Feliu A, Masana L, Plana N, Group D Plasma inducible degrader of the LDLR, soluble low-density lipoprotein receptor, and proprotein convertase subtilisin/kexin type 9 levels as potential biomarkers of familial hypercholesterolemia in children. J Clin Lipidol. 2018;12:211–218. doi: 10.1016/j.jacl.2017.10.003. - DOI - PubMed

[10] Girona J, Rodriguez-Borjabad C, Ibarretxe D, Heras M, Amigo N, Feliu A, Masana L, Plana N, Group D Plasma inducible degrader of the LDLR, soluble low-density lipoprotein receptor, and proprotein convertase subtilisin/kexin type 9 levels as potential biomarkers of familial hypercholesterolemia in children. J Clin Lipidol. 2018;12:211–218. doi: 10.1016/j.jacl.2017.10.003. - DOI - PubMed

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The enigma of soluble LDLR: could inflammation be the key?

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The enigma of soluble LDLR: could inflammation be the key?

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