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Updated: May 5, 2026
Quantitative Analysis of Cellular Composition in Advanced Atherosclerotic Lesions of Smooth Muscle Cell Lineage-Tracing Mice
Published on: February 20, 2019
Targeted disruption of the class B scavenger receptor CD36 protects against atherosclerotic lesion development in
M Febbraio1, E A Podrez, J D Smith
1Department of Medicine, Division of Hematology and Medical Oncology, Center of Vascular Biology, Weill Medical College of Cornell University, New York, New York 10021, USA. mjfebbra@med.cornell.edu
Insights
The scavenger receptor CD36 plays a significant role in atherosclerosis development. Removing CD36 substantially reduced atherosclerotic lesions in mice, indicating its potential as a therapeutic target.
Area of Science:
- Cardiovascular Biology
- Immunology
- Metabolic Diseases
Background:
- Macrophage scavenger receptors are crucial in atherosclerosis pathogenesis.
- CD36, a class B scavenger receptor, is implicated in lipid uptake by macrophages.
Purpose of the Study:
- To investigate the specific role of CD36 in the development of atherosclerosis.
- To determine if CD36 deficiency impacts lesion progression in a proatherogenic setting.
Main Methods:
- Generated CD36-apo E double-null mice by crossing CD36-null and apo E-null strains.
- Quantified aortic tree and aortic sinus lesion development under Western diet and normal chow conditions.
- Assessed copper-oxidized LDL and modified LDL uptake and in vitro lipid accumulation in macrophages.
Main Results:
- CD36-apo E double-null mice exhibited a 76.5% decrease in aortic tree lesions (Western diet) and a 45% decrease in aortic sinus lesions (normal chow).
- Macrophages from double-null mice showed over 60% less binding and internalization of modified LDL.
- In vitro lipid accumulation and foam cell formation were significantly inhibited.
Conclusions:
- CD36 plays a major role in in vivo atherosclerotic lesion development.
- CD36 blockade demonstrates protective effects, even under severe proatherogenic conditions.
- Targeting CD36 may offer a therapeutic strategy for atherosclerosis.
Abstract:
Macrophage scavenger receptors have been implicated as key players in the pathogenesis of atherosclerosis. To assess the role of the class B scavenger receptor CD36 in atherogenesis, we crossed a CD36-null strain with the atherogenic apo E-null strain and quantified lesion development. There was a 76.5% decrease in aortic tree lesion area (Western diet) and a 45% decrease in aortic sinus lesion area (normal chow) in the CD36-apo E double-null mice when compared with controls, despite alterations in lipoprotein profiles that often correlate with increased atherogenicity. Macrophages derived from CD36-apo E double-null mice bound and internalized more than 60% less copper-oxidized LDL and LDL modified by monocyte-generated reactive nitrogen species. A similar inhibition of in vitro lipid accumulation and foam cell formation after exposure to these ligands was seen. These results support a major role for CD36 in atherosclerotic lesion development in vivo and suggest that blockade of CD36 can be protective even in more extreme proatherogenic circumstances.
