English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Mice deficient in both macrophage-colony-stimulating factor (M-CSF, op) and apolipoprotein E (apoE) have elevated cholesterol levels but are protected from atherosclerosis. To assess the contribution of macrophage (Mphi) phenotypic heterogeneity and scavenger receptor (SR-A) expression to this seeming paradox, we characterized the Mphi phenotype by immunohistochemistry in these animals. Lesion size was determined in animals fed a chow or Western-type diet, and lipoprotein clearance studies were performed in vivo. Op0/E0 mice have fourfold smaller aortic root lesions than op2/E0 animals despite 2.5-fold higher total plasma cholesterol levels. Mphis in atherosclerotic lesions of op2/E0 mice constitute a predominantly recruited and M-CSF-dependent population. In addition, Mphis in different locations in plaques show phenotypic heterogeneity. SR-A expression in op0/E0 mice is reduced in proportion to the decrease in Mphi numbers, and M-CSF is thus not an essential requirement for SR-A expression in vivo. M-CSF-deficient mice degrade injected AcLDL , showing an adequate level of SR-A activity present in vivo. In contrast, beta-VLDL clearance in op0/E0 mice is decreased, implicating monocytes/Mphis in its catabolism. There is prominent lipid accumulation in op2/E0 Kupffer cells and hepatocytes but not in M-CSF-independent Kupffer Mphis from op0/E0 mice. SR-A, while abundantly expressed on both Kupffer cells and sinusoidal endothelial cells in op2/E0 mice, remains mainly on sinusoidal endothelial cells in op0/E0 mice. This may explain preservation of SR-A activity in these animals. Our findings clearly illustrate the importance of both M-CSF and M-CSF-dependent monocytes/Mphis in maintaining cholesterol homeostasis and in atherogenesis.

Macrophage Phenotype in Mice Deficient in Both Macrophage-Colony–Stimulating Factor (Op) and Apolipoprotein E