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Complete deficiency of the low-density lipoprotein receptor is associated with increased apolipoprotein B-100 production.
Arterioscler Thromb Vasc Biol. 2005 Mar; 25(3):560-5.AT

Abstract

OBJECTIVE

We addressed the role of the low-density lipoprotein (LDL) receptor in determining clearance rates and production rate (PR) of apolipoprotein B (apoB) in humans.

METHODS AND RESULTS

Kinetic studies using endogenous labeling of apoB with deuterated leucine were performed in 7 genetically defined patients with homozygous familial hypercholesterolemia (FH) and compared with 4 controls. The fractional catabolic rates (FCR) and PRs for apoB were determined by multicompartmental modeling. The FCRs of very-low-density lipoprotein 1 (VLDL1), VLDL2, intermediate-density lipoprotein (IDL), and LDL apoB were lower in FH than in controls, with the LDL apoB FCR being significantly lower (0.148+/-0.049 versus 0.499+/-0.099 pools x d(-1); P=0.008). Whereas receptor-defective FH patients had a total apoB PR similar to controls, receptor-null FH patients had a significantly greater total apoB PR than controls (35.97+/-10.51 versus 21.32+/-4.21 mg x kg(-1) x d(-1), respectively; P=0.02).

CONCLUSIONS

This first study of apoB metabolism in homozygous FH using endogenous labeling with stable isotopes demonstrates that the LDL receptor contributes significantly to the clearance of LDL from plasma but plays a lesser role in the clearance of larger apoB-containing lipoproteins. Furthermore, these data also indicate that absence of a LDL receptor in humans substantially influences the apoB PR in vivo.

Authors+Show Affiliations

Department of Medicine, University of Pennsylvania, 644 BRB II/III, 421 Curie Blvd, Philadelphia, PA 19104, USA. jsmillar@mail.med.upenn.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

15637307

Citation

Millar, John S., et al. "Complete Deficiency of the Low-density Lipoprotein Receptor Is Associated With Increased Apolipoprotein B-100 Production." Arteriosclerosis, Thrombosis, and Vascular Biology, vol. 25, no. 3, 2005, pp. 560-5.
Millar JS, Maugeais C, Ikewaki K, et al. Complete deficiency of the low-density lipoprotein receptor is associated with increased apolipoprotein B-100 production. Arterioscler Thromb Vasc Biol. 2005;25(3):560-5.
Millar, J. S., Maugeais, C., Ikewaki, K., Kolansky, D. M., Barrett, P. H., Budreck, E. C., Boston, R. C., Tada, N., Mochizuki, S., Defesche, J. C., Wilson, J. M., & Rader, D. J. (2005). Complete deficiency of the low-density lipoprotein receptor is associated with increased apolipoprotein B-100 production. Arteriosclerosis, Thrombosis, and Vascular Biology, 25(3), 560-5.
Millar JS, et al. Complete Deficiency of the Low-density Lipoprotein Receptor Is Associated With Increased Apolipoprotein B-100 Production. Arterioscler Thromb Vasc Biol. 2005;25(3):560-5. PubMed PMID: 15637307.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Complete deficiency of the low-density lipoprotein receptor is associated with increased apolipoprotein B-100 production. AU - Millar,John S, AU - Maugeais,Cyrille, AU - Ikewaki,Katsunori, AU - Kolansky,Daniel M, AU - Barrett,P Hugh R, AU - Budreck,Elaine C, AU - Boston,Raymond C, AU - Tada,Norio, AU - Mochizuki,Seibu, AU - Defesche,Joep C, AU - Wilson,James M, AU - Rader,Daniel J, Y1 - 2005/01/06/ PY - 2005/1/8/pubmed PY - 2005/11/9/medline PY - 2005/1/8/entrez SP - 560 EP - 5 JF - Arteriosclerosis, thrombosis, and vascular biology JO - Arterioscler. Thromb. Vasc. Biol. VL - 25 IS - 3 N2 - OBJECTIVE: We addressed the role of the low-density lipoprotein (LDL) receptor in determining clearance rates and production rate (PR) of apolipoprotein B (apoB) in humans. METHODS AND RESULTS: Kinetic studies using endogenous labeling of apoB with deuterated leucine were performed in 7 genetically defined patients with homozygous familial hypercholesterolemia (FH) and compared with 4 controls. The fractional catabolic rates (FCR) and PRs for apoB were determined by multicompartmental modeling. The FCRs of very-low-density lipoprotein 1 (VLDL1), VLDL2, intermediate-density lipoprotein (IDL), and LDL apoB were lower in FH than in controls, with the LDL apoB FCR being significantly lower (0.148+/-0.049 versus 0.499+/-0.099 pools x d(-1); P=0.008). Whereas receptor-defective FH patients had a total apoB PR similar to controls, receptor-null FH patients had a significantly greater total apoB PR than controls (35.97+/-10.51 versus 21.32+/-4.21 mg x kg(-1) x d(-1), respectively; P=0.02). CONCLUSIONS: This first study of apoB metabolism in homozygous FH using endogenous labeling with stable isotopes demonstrates that the LDL receptor contributes significantly to the clearance of LDL from plasma but plays a lesser role in the clearance of larger apoB-containing lipoproteins. Furthermore, these data also indicate that absence of a LDL receptor in humans substantially influences the apoB PR in vivo. SN - 1524-4636 UR - https://www.unboundmedicine.com/medline/citation/15637307/Complete_deficiency_of_the_low_density_lipoprotein_receptor_is_associated_with_increased_apolipoprotein_B_100_production_ L2 - http://www.ahajournals.org/doi/full/10.1161/01.ATV.0000155323.18856.a2?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -