title: Altered apolipoprotein A-V expression during the acute phase response is independent of plasma triglyceride levels in mice and humans.
abstract: Plasma triglyceride (TG) levels are altered during the acute phase response (APR). Plasma levels of the recently discovered apolipoprotein A-V (apoA-V) are inversely associated with plasma TG. The aim of this study was to investigate the change of apoA-V plasma levels and hepatic apoA-V expression during the APR in relation to plasma TG. During human APR plasma apoA-V was decreased as were plasma TG (each P<0.01). Also early in the course of the murine APR plasma apoA-V levels and hepatic apoA-V expression were decreased and changed in the same direction as plasma TG. Treatment of HepG2 cells with TNF-alpha and IL-1beta decreased apoA-V mRNA levels early by 42% and 55%, respectively (each P<0.001). However, in promoter/reporter assays the human apoA-V promoter was unresponsive to proinflammatory cytokines. Instead, we demonstrate that a significant decrease in apoA-V mRNA stability in response to treatment with TNF-alpha and IL-1beta is the underlying basis of decreased apoA-V expression during the APR (P<0.05). These data demonstrate that (i) apoA-V expression decreases early during the APR due to changes in mRNA stability, and (ii) during the APR apoA-V is not inversely related to plasma TG levels in mice and humans, thereby identifying a relevant pathophysiological setting, in which the previously reported close inverse association between these parameters does not hold true.
authors.affiliation: Department of Medicine, Charité Campus Mitte, Berlin, Germany.
authors.forename: Steffi
authors.initials: S
authors.lastname: Becker
authors.forename: Lutz
authors.initials: L
authors.lastname: Schomburg
authors.forename: Kostja
authors.initials: K
authors.lastname: Renko
authors.forename: Markus
authors.initials: M
authors.lastname: Tölle
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* / Q000276:immunology*; D000368:Aged; D000818:Animals; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000097:blood* / Q000276:immunology*; D001054:Apolipoproteins A; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000097:blood*
chemical_list: C437704:APOA5 protein, human; C499058:Apoa5 protein, mouse; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A; D014280:Triglycerides