Expression of human secretory group IIA phospholipase A2 is associated with reduced concentrations of plasma cholesterol in transgenic mice

被引:8
作者
Menschikowski, M
Eckey, P
Pietzsch, J
Aufenanger, J
Kumpf, R
Nelz, P
Jaross, W
机构
[1] Tech Univ, Fac Med, Inst Clin Chem & Lab Med, Dresden, Germany
[2] Tech Univ, Fac Med, Inst & Policlin Clin Metab Res, Dresden, Germany
[3] Klinikum Ingolstadt, Inst Lab Med, Dresden, Germany
[4] Tech Univ, Fac Med, Expt Ctr, Dresden, Germany
关键词
D O I
10.1023/A:1007061413234
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
It is well known that acute and chronic inflammatory reactions are accompanied by markedly decreased concentrations of plasma total cholesterol. However, the mechanisms underlying this hypocholesterolemia are not yet completely understood. To explore the question of whether an increased serum activity of secretory group IIA phospholipase A(2) (sPLA(2)) may contribute to the development of hypocholesterolemia during inflammation, the lipids and lipoprotein patterns in the plasma of transgenic mice overexpressing the human sPLA(2) gene were studied and compared with those of nontransgenic controls. The mean plasma enzyme activities determined by using [C-14]-oleate labeled Escherichia coli-membranes were found to be 331 +/- 262 U/1 in transgenic mice while the catalytic activity in plasma of controls was below the analytical sensitivity of the assay (0.5 U/1). Compared to nontransgenic littermates, sPLA(2)-transgenic mice exhibited significantly lower plasma concentrations of total cholesterol (2.53 +/- 0.37 mmol/l vs. 3.49 +/- 0.44 mmol/l, p < 0.0001). The reduction of total cholesterol was due to decreased HDL and LDL cholesterol levels (1.21 +/- 0.10 mmol/l vs. 1.78 +/- 0.37 mmol/l, and 0.28 +/- 0.02 mmol/l vs. 0.69 +/- 0.23 mmol/l, respectively p < 0.05). The analysis of lipoprotein composition indicated that the LDL of transgenic mice were selectively depleted in free and esterified cholesterol, whereas HDL of the two animal groups contained comparable percentages of cholesterol. The triglycerides were significantly enriched in LDL and HDL, but tended to be less in VLDL of transgenic mice. In conclusion, the results of the study have demonstrated that the expression of sPLA(2) may influence the metabolism of lipoproteins, possibly contributing to the development of hypocholesterolemia during inflammation.
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页码:227 / 237
页数:11
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