Myeloperoxidase and serum amyloid A contribute to impaired in vivo reverse cholesterol transport during the acute phase response but not group IIA secretory phospholipase A2[S]

Journal of Lipid Research

Niels Nijstad¹  Markus van der Giet²  Ruben V.C. Buijs³  Wijtske Annema³  Markus Tölle³  Peter Heeringa³  Uwe J.F. Tietge⁴  Jan Freark de Boer⁴ 

[1] Top Institute Food and Nutrition, Wageningen The Netherlands;Department of Pathology and Medical Biology, University Medical Center Groningen Groningen The Netherlands;Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen Groningen The Netherlands;Medizinische Klinik IV–Nephrology, Charite–Campus Benjamin Franklin, Berlin, Germany;

关键词: feces;    inflammation;    sepsis;    atherosclerosis;    mice;   

DOI  :  

来源: DOAJ

【 摘 要 】

Atherosclerosis is linked to inflammation. HDL protects against atherosclerotic cardiovascular disease, mainly by mediating cholesterol efflux and reverse cholesterol transport (RCT). The present study aimed to test the impact of acute inflammation as well as selected acute phase proteins on RCT with a macrophage-to-feces in vivo RCT assay using intraperitoneal administration of [3H]cholesterol-labeled macrophage foam cells. In patients with acute sepsis, cholesterol efflux toward plasma and HDL were significantly decreased (P < 0.001). In mice, acute inflammation (75 µg/mouse lipopolysaccharide) decreased [3H]cholesterol appearance in plasma (P < 0.05) and tracer excretion into feces both within bile acids (−84%) and neutral sterols (−79%, each P < 0.001). In the absence of systemic inflammation, overexpression of serum amyloid A (SAA, adenovirus) reduced overall RCT (P < 0.05), whereas secretory phospholipase A2 (sPLA2, transgenic mice) had no effect. Myeloperoxidase injection reduced tracer appearance in plasma (P < 0.05) as well as RCT (−36%, P < 0.05). Hepatic expression of bile acid synthesis genes (P < 0.01) and transporters mediating biliary sterol excretion (P < 0.01) was decreased by inflammation. In conclusion, our data demonstrate that acute inflammation impairs cholesterol efflux in patients and macrophage-to-feces RCT in vivo in mice. Myeloperoxidase and SAA contribute to a certain extent to reduced RCT during inflammation but not sPLA2. However, reduced bile acid formation and decreased biliary sterol excretion might represent major contributing factors to decreased RCT in inflammation.

【 授权许可】

Unknown