title: Myeloperoxidase and serum amyloid A contribute to impaired in vivo reverse cholesterol transport during the acute phase response but not group IIA secretory phospholipase A(2).
abstract: 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 [(3)H]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 microg/mouse lipopolysaccharide) decreased [(3)H]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 A(2) (sPLA(2), 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 sPLA(2). However, reduced bile acid formation and decreased biliary sterol excretion might represent major contributing factors to decreased RCT in inflammation.
authors.affiliation: Department of Pediatrics, Center for Liver, Digestive, and Metabolic Diseases, University Medical Center Groningen, Groningen, The Netherlands.
authors.forename: Wijtske
authors.initials: W
authors.lastname: Annema
authors.forename: Niels
authors.initials: N
authors.lastname: Nijstad
authors.forename: Markus
authors.initials: M
authors.lastname: Tölle
authors.forename: Jan Freark
authors.initials: JF
authors.lastname: de Boer
authors.forename: Ruben V C
authors.initials: RV
authors.lastname: Buijs
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
authors.forename: Markus
authors.initials: M
authors.lastname: van der Giet
authors.forename: Uwe J F
authors.initials: UJ
authors.lastname: Tietge
mesh_terms: D000210:Acute-Phase Reaction / Q000097:blood / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D050197:Atherosclerosis / Q000503:physiopathology / Q000517:prevention & control; D001692:Biological Transport; D002478:Cells, Cultured; D002784:Cholesterol / Q000097:blood / Q000378:metabolism*; D005243:Feces / Q000737:chemistry; D005487:Foam Cells / Q000378:metabolism; D054501:Group II Phospholipases A2 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008875:Middle Aged; D009195:Peroxidase / Q000008:administration & dosage / Q000097:blood / Q000302:isolation & purification / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D018805:Sepsis / Q000097:blood; D000685:Serum Amyloid A Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D013256:Steroids / Q000378:metabolism
chemical_list: D008055:Lipids; D008074:Lipoproteins; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D013256:Steroids; D002784:Cholesterol; D009195:Peroxidase; D054501:Group II Phospholipases A2