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Updated: Jun 25, 2026

Quantification of Atherosclerosis in Mice
Published on: June 12, 2019
Tissue-specific roles of ABCA1 influence susceptibility to atherosclerosis
Liam R Brunham1, Roshni R Singaraja, MyNgan Duong
1Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada.
Insights
ATP-binding cassette transporter A1 (ABCA1) influences atherosclerosis. Hepatic ABCA1 expression protects against atherosclerosis, while macrophage ABCA1 deletion shows no significant effect on disease progression.
Area of Science:
- Cardiovascular Biology
- Lipid Metabolism
- Atherosclerosis Research
Background:
- ATP-binding cassette transporter, subfamily A, member 1 (ABCA1) is crucial for HDL cholesterol metabolism.
- The precise role of ABCA1 in atherosclerosis susceptibility remains debated.
Purpose of the Study:
- To investigate the role of ABCA1 in atherosclerosis using genetic models.
- To determine the specific contributions of ABCA1 in different tissues to atherogenesis.
Main Methods:
- Utilized transgenic overexpression of human ABCA1 in Ldlr(-/-) mice.
- Employed tissue-specific Abca1 inactivation in Apoe(-/-) and Ldlr(-/-) mouse models.
- Assessed atherosclerosis development and HDL cholesterol levels.
Main Results:
- ABCA1 overexpression reduced atherosclerosis in Ldlr(-/-) mice.
- Hepatic Abca1 deficiency in Apoe(-/-) mice led to lower HDL cholesterol and accelerated atherosclerosis.
- Macrophage-specific Abca1 deletion in Ldlr(-/-) mice did not alter atherosclerotic lesion area.
Conclusions:
- Physiological ABCA1 expression modulates atherosclerosis susceptibility.
- Hepatic ABCA1 is a key site for atheroprotection.
- Selective deletion of macrophage ABCA1 does not significantly impact atherogenesis.
Objective:
The ATP-binding cassette transporter, subfamily A, member 1 (ABCA1) plays a key role in HDL cholesterol metabolism. However, the role of ABCA1 in modulating susceptibility to atherosclerosis is controversial.
Methods And Results:
We investigated the role of ABCA1 in atherosclerosis using a combination of overexpression and selective deletion models. First, we examined the effect of transgenic overexpression of a full-length human ABCA1-containing bacterial artificial chromosome (BAC) in the presence or absence of the endogenous mouse Abca1 gene. ABCA1 overexpression in the atherosclerosis-susceptible Ldlr(-/-) background significantly reduced the development of atherosclerosis in both the presence and absence of mouse Abca1. Next, we used mice with tissue-specific inactivation of Abca1 to dissect the discrete roles of Abca1 in different tissues on susceptibility to atherosclerosis. On the Apoe(-/-) background, mice lacking hepatic Abca1 had significantly reduced HDL cholesterol and accelerated atherosclerosis, indicating that the liver is an important site at which Abca1 plays an antiatherogenic role. In contrast, mice with macrophage-specific inactivation of Abca1 on the Ldlr(-/-) background displayed no change in atherosclerotic lesion area.
Conclusions:
These data indicate that physiological expression of Abca1 modulates the susceptibility to atherosclerosis and establish hepatic Abca1 expression as an important site of atheroprotection. In contrast, we show that selective deletion of macrophage Abca1 does not significantly modulate atherogenesis.
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