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Role of CD36, the macrophage class B scavenger receptor, in atherosclerosis
A C Nicholson1, J Han, M Febbraio
1Center of Vascular Biology, Cornell University Medical College, New York, New York 10021, USA.
Insights
CD36 is crucial in atherosclerosis development, driving macrophage foam cell formation. Removing CD36 significantly reduced atherosclerotic lesions in mice, highlighting its therapeutic potential.
Area of Science:
- Cardiovascular Research
- Immunology
- Molecular Biology
Background:
- Atherosclerosis pathogenesis involves macrophage uptake of modified LDL and foam cell formation.
- Scavenger receptors, notably CD36, play a key role in early disease progression.
- Genetically engineered mouse models are vital for studying scavenger receptor contributions.
Purpose of the Study:
- To elucidate the role of CD36 in macrophage foam cell development and atherosclerotic lesion progression in vivo.
- To investigate the regulation of CD36 expression in response to oxidized LDL (OxLDL).
- To assess the therapeutic potential of targeting CD36 in atherosclerosis.
Main Methods:
- Utilized genetically engineered ApoE null mice lacking CD36.
- Fed mice a Western diet to induce atherosclerosis.
- Analyzed atherosclerotic lesion area and CD36 expression.
Main Results:
- Absence of CD36 led to a 70% reduction in total atherosclerotic lesion area in ApoE null mice on a Western diet.
- Oxidized LDL (OxLDL) was shown to induce CD36 gene expression, stimulating its own uptake.
- OxLDL-induced CD36 upregulation involves the activation of the transcription factor PPAR-gamma.
Conclusions:
- CD36 plays a major role in macrophage foam cell development and atherosclerotic lesion progression.
- Targeting CD36 presents a promising therapeutic strategy for atherosclerosis.
- Understanding CD36 regulation by OxLDL and PPAR-gamma offers insights into disease mechanisms.
Abstract:
Recent work in the field of atherosclerosis has greatly expanded our knowledge of the pathogenesis of this disease. Scavenger receptors, including CD36, are thought to be most important early in the disease progression during macrophage uptake of modified LDL and foam cell formation. Genetically engineered murine models have been used to elucidate the contribution of the different scavenger receptors, to identify specific ligands related to LDL modifications, and to assess the possible therapeutic ramifications of targeting scavenger receptors. We have demonstrated a major role for CD36 in macrophage foam cell development and subsequent lesion development in vivo. Absence of CD36 in an atherogenic Apo E null background resulted in a 70% decrease in total lesion area in Western diet-fed mice. We have also made significant progress in our understanding of the regulation of expression of CD36 and have demonstrated that OxLDL can stimulate its own uptake by induction of CD36 gene expression. The mechanism by which OxLDL upregulates CD36 involves activation of the transcription factor, PPAR-gamma.