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SPA Promotes Atherosclerosis Through Mediating Macrophage Foam Cell Formation-Brief Report
Skylar D King1, Dunpeng Cai1, Alisha Pillay2
1Department of Surgery (S.D.K., D.C., M.M.F., S.-Y.C.), University of Missouri School of Medicine, Columbia.
Surfactant protein A (SPA) promotes atherosclerosis by increasing macrophage foam cell formation and CD36 expression. SPA deficiency attenuates atherosclerosis and reduces foam cell accumulation in mice.
Area of Science:
- Cardiovascular Research
- Immunology
- Molecular Biology
Background:
- Atherosclerosis is an inflammatory disease where macrophage foam cells are key.
- Surfactant protein A (SPA) regulates macrophage function in inflammation.
- The role of SPA in atherosclerosis and foam cell formation is unknown.
Purpose of the Study:
- To investigate the role of SPA in atherosclerosis.
- To determine SPA's effect on macrophage foam cell formation.
Main Methods:
- Assessed SPA expression in human and mouse atherosclerotic arteries.
- Utilized wild-type and SPA-deficient mice fed high-fat diets.
- Conducted in vitro studies with macrophages to assess foam cell formation.
Main Results:
- SPA expression is elevated in atherosclerotic lesions.
- SPA deficiency reduced hypercholesterolemia, atherosclerosis, and foam cell number.
- SPA deficiency decreased intracellular cholesterol and foam cell formation, downregulating CD36.
- SPA increased CD36 expression in human macrophages.
Conclusions:
- SPA is a novel factor promoting atherosclerosis.
- SPA enhances foam cell formation and atherosclerosis by increasing scavenger receptor CD36 expression.
- This leads to increased cellular oxidized low-density lipoprotein (OxLDL) uptake.
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