HDLs in apoA-I transgenic Abca1 knockout mice are remodelednormally in plasma but are hypercatabolized by the kidney.
Patients homozygous for Tangier disease have a near absence of plasma HDL as a result of mutations in ABCA1 and hypercatabolize normal HDL particles. To determine the relationship between ABCA1 expression and HDL catabolism, we investigated intravascular remodeling, plasma clearance, and organ-specific uptake of HDL in mice expressing the human apolipoprotein A-I (apoA-I) transgene in the Abca1 knockout background. Small HDL particles (7.5 nm), radiolabeled with 125I-tyramine cellobiose, were injected into recipient mice to quantify plasma turnover and the organ uptake of tracer. Small HDL tracer was remodeled to 8.2 nm diameter particles within 5 min in human apolipoprotein A-I transgenic (hA-ITg) mice (control) and knockout mice. Decay of tracer from plasma was 1.6-fold more rapid in knockout mice (P<0.05) and kidney uptake was twice that of controls, with no difference in liver uptake. We also observed 2-fold greater hepatic expression of ABCA1 protein in hA-ITg mice compared with nontransgenic mice, suggesting that overexpression of human apoA-I stabilized hepatic ABCA1 protein in vivo.
- Research Organization:
- Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
- Sponsoring Organization:
- USDOE Director. Office of Science. Office of Biological andEnvironmental Research; National Institutes of Health Grants HL-049373and HL-054176 and HL-07115
- DOE Contract Number:
- AC02-05CH11231
- OSTI ID:
- 899550
- Report Number(s):
- LBNL--60375; BnR: KP1103010
- Journal Information:
- Journal of Lipid Research, Journal Name: Journal of Lipid Research Vol. 46; ISSN 0022-2275; ISSN JLPRAW
- Country of Publication:
- United States
- Language:
- English
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