Inflammatory stress promotes lipid accumulation in the aorta and liver of SR-A/CD36 double knock-out mice

Abstract

Abstract. Macrophage scavenger receptors (Srs), particularly type a Sr (Sr-a) and cd36, have been implicated in binding and internalizing modified forms of low-density lipoprotein (ldl) through a mechanism not regulated by cellular cholesterol content, resulting in cholesterol accumulation and foam cell formation. To test the impact of the absence of these receptors on lipid-mediated injuries in aortas or livers under inflammatory stress, C57BL/6 mice with knocked out SR-A and CD36 (SR DKO) were administered a combination of a high-fat diet and casein injection for 14 weeks. We analyzed the lipid accumulation in the aortas and livers, assessing lipid droplets, circulating inflammatory cytokines, serum lipid levels and gene expression of cholesterol uptake. Lipid accumulation in the aortas and livers of the inflammatory mice were assessed by morphologic and quantitative assay of cholesterol ester in the livers. The SR DKO mice under inflammatory stress showed an increased level of serum amyloid A, but did not exhibit any significantly increased levels of TNF-α and IL-6, while morphological analysis revealed a significant increase in lipid accumulation in the aortas and livers of the inflammatory mice. Although SR DKO mice exhibit substantially reduced inflammatory cytokine factors, loss of the SR pathway does accelerate lipid accumulation through LDL receptor pathways to lipid accumulation. These data suggest that targeted inhibition of SR pathways in vivo may promote lipid-mediated injuries in aortas and livers under inflammatory stress.

On Detecting Incomplete Soft or Hard Selective Sweeps Using Haplotype Structure

“…Also, it may play a role in lipid exchange and transport throughout the body, as well as in reverse cholesterol transport from peripheral cells to the liver (Duchateau et al 2000). CD 36 is implicated in the binding and internalization of oxidized low-density lipoprotein (Ox-LDL) (Liu et al 2010). It is involved in cholesterol uptake in monocytes and macrophages (Anwar et al 2011) and contributes to cholesterol efflux in hepatic cells (Truong et al 2010).…”

“…Variants in this gene have been shown to be associated with increased HDL cholesterol levels (Liu et al 2010). In addition, variants in the gene are also associated with malaria resistance (Aitman et al 2000; Sirugo et al 2008).…”

Comparative Studies of Vertebrate Platelet Glycoprotein 4 (CD36)

“…Human CD36 is expressed at very high levels in various cells and tissues of the body, including platelets, monocytes/macrophages, and microvascular endothelial cells, plays important roles in atherosclerosis, inflammation, thrombosis and angiogenesis [4,6,7,30,31,32], and is upregulated in human monocytes following statin administration [33]. Studies of Cd36¯/Cd36¯ knockout mice have shown that CD36 -deficiency protects against Western-type diet related cardiac dysfunction [34,35,36] and contributes to a reduction in fatty acid oxidation by muscle mitochondria [11,37]. Human clinical studies have also examined CD36 polymorphisms associated with enhanced atherosclerotic cardiovascular diseases [38,39], type II diabetes [9], oral fat perception, fat preference and obesity in African-Americans [40] and protection from malaria [41,42].…”