Increased hepatic cholesterol accumulation in transgenic mice overexpressing human secretory phospholipase A2 group IIA.
It has been demonstrated in transgenic mice that the overexpression of human phospholipase A2 group IIA (sPLA2), an acute-phase reactant, is associated with depressed plasma cholesterol levels, altered lipoprotein compositions, and increased lipid depositions in aortic walls. It was the aim of the present study to investigate whether the reduced plasma cholesterol levels in sPLA2-transgenic mice may be due to an increased transfer of lipids from sPLA2-modified lipoproteins to the liver and/or other nonvascular tissues. Ten sPLA2-transgenic mice and an equal number of nontransgenic littermates were fed a cholesterol-enriched (1%) diet for 13 weeks. After autopsy, cholesterol and triglyceride concentrations were measured in homogenates of liver, spleen, kidney, and myocardial tissues. Compared to the nontransgenic controls, the sPLA2-transgenic mice exhibited significantly lower plasma cholesterol levels, which was due to a reduction in both HDL and beta-lipoprotein (LDL + beta-VLDL) cholesterol. Liver tissues from the transgenic mice were found to contain significantly increased concentrations of free and esterified cholesterol, which was not associated with increased triglyceride concentrations. Spleen, kidney, and heart tissues of the two animal groups showed no significant differences in cholesterol or triglyceride concentrations. The findings suggest that the overexpression of human secretory phospholipase A2 group IIA leads to an enhanced delivery of cholesterol from phospholipolysed lipoproteins to the liver. This mechanism is likely to contribute to the development of hypocholesterolemia observed in patients with inflammatory diseases.
Eckey
Rolf
R
Institute for Clinical Chemistry and Laboratory Medicine, Medical Faculty, Technical University of Dresden, Dresden, Germany. R.Eckey@r-eckey.de
Menschikowski
Mario
M
Lattke
Peter
P
Jaross
Werner
W
D000818:Animals; D002791:Cholesterol, Dietary / Q000097:blood / Q000493:pharmacokinetics*; D005247:Feeding Behavior; D015870:Gene Expression; D054501:Group II Phospholipases A2; D006801:Humans; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010741:Phospholipases A / Q000235:genetics* / Q000378:metabolism*; D054467:Phospholipases A2; D014280:Triglycerides / Q000378:metabolism
D002791:Cholesterol, Dietary; D014280:Triglycerides; D010741:Phospholipases A; D054501:Group II Phospholipases A2; D054467:Phospholipases A2