In:
Arteriosclerosis, Thrombosis, and Vascular Biology, Ovid Technologies (Wolters Kluwer Health), Vol. 43, No. Suppl_1 ( 2023-05)
Abstract:
Aim: SR-BI null mice are known to have abnormally large HDL enriched in free cholesterol. Here, we examined the involvement of apoA-I on high free cholesterol-HDL in SR-BI null mice plasma. Method: Mice with SR-BI null allele and ApoA-I null allele were generated by mating CAG-cre tg mice to their floxed mice. By crossing these mice, ApoA-I/SR-BI double null mice were obtained. The gel permeability HPLC-based plasma lipoprotein profile of the mouse was analyzed by LipoSEARCH (Immuno-Biological Laboratories, Co. Ltd., Japan). Results: In ApoA-I null mice plasma, HDL is low but relatively larger in particle diameters than wild-type mice which have similar characteristics to SR-BI null mice. In the ApoA-I / SR-BI double null mice, large HDL/ very small LDL (13-19 nm) was increased to 1.86-fold. Free cholesterol content in the ApoA-I / SR-BI double null mice was increased in 12 nm to 60 nm size lipoprotein particles. Free cholesterol levels in the large and the very large HDL fraction (12 to 16 nm), the LDL fraction (16 to 30 nm), and the VLDL fraction (30 to 70 nm) were 1.16, 2.38, and 2.36 mg/dL in Apoa1 -/- mice, and were 18.81, 44.02, and 15.56 mg/dL in Scarb1 -/- :Apoa1 -/- mice, respectively. Conclusions: ApoA-I null mice plasma profile in free cholesterol level was dramatically increased by deletion of Scarb1 . High free cholesterol in plasma is known as an atherosclerotic factor. High free cholesterol in these large lipoprotein particles may explain by LCAT function is perhaps only effective on the normal size HDL or disc shape HDL with apoA-I. On the other hand, CETP tg/ SR-BI null mice with normal HDL size also show high free cholesterol HDL(ATVB 2010, Hildebrand et al. ). Furthermore, Wolman’s Disease, deficiency of lipase in the lysosome, did not change cholesterol homeostasis of taken-up cholesterol from HDL (BBA 1990, Sparrow and Pittman). Further study is necessary to identify the true origin of plasma-free cholesterol in SR-BI null mice plasma.
Type of Medium:
Online Resource
ISSN:
1079-5642
,
1524-4636
DOI:
10.1161/atvb.43.suppl_1.680
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2023
detail.hit.zdb_id:
1494427-3
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