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bioRxiv · 10.1101/2023.03.23.533959

Surfactant protein A promotes atherosclerosis through mediating macrophage foam cell formation

King, S. D.·Cai, D.·Fraunfelder, M. M.·Chen, S.-Y.
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Abstract

BACKGROUNDAtherosclerosis is a progressive inflammatory disease where macrophage foam cells play a central role in the pathogenesis. Surfactant protein A (SPA) is a lipid-associating protein involved with regulating macrophage function in various inflammatory diseases. However, the role of SPA in atherosclerosis and macrophage foam cell formation has not been investigated. METHODSPrimary resident peritoneal macrophages were extracted from wildtype (WT) and SPA deficient (SPA-/-) mice to determine the functional effects of SPA in macrophage foam cell formation. SPA expression was assessed in healthy vessels and atherosclerotic aortic tissue from the human coronary artery and WT or apolipoprotein e-deficient (ApoE-/-) mice brachiocephalic arteries fed high fat diets (HFD) for 4 weeks. Hypercholesteremic WT and SPA-/- mice fed a HFD for 6 weeks were investigated for atherosclerotic lesions in vivo. RESULTSIn vitro experiments revealed that global SPA deficiency reduced intracellular cholesterol accumulation and macrophage foam cell formation. Mechanistically, SPA-/- dramatically decreased CD36 cellular and mRNA expression. SPA expression was increased in atherosclerotic lesions in humans and ApoE-/- mice. In vivo SPA deficiency attenuated atherosclerosis and reduced the number of lesion-associated macrophage foam cells. CONCLUSIONSOur results elucidate that SPA is a novel factor for atherosclerosis development. SPA enhances macrophage foam cell formation and atherosclerosis through increasing scavenger receptor cluster of differentiation antigen 36 (CD36) expression.

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King, S. D., Cai, D., Fraunfelder, M. M., Chen, S.-Y.. 2023-03-24. Surfactant protein A promotes atherosclerosis through mediating macrophage foam cell formation. https://doi.org/10.1101/2023.03.23.533959

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