出版社：American Society for Biochemistry and Molecular Biology
摘要：In this work, we investigated the impact of testosterone deficiencyand cholesteryl ester transfer protein (CETP) expression onlipoprotein metabolism and diet-induced atherosclerosis. CETPtransgenic mice and nontransgenic (nTg) littermates were studied4 weeks after bilateral orchidectomy or sham operation. Castratedmice had an increase in the LDL fraction (+36% for CETP and+79% for nTg mice), whereas the HDL fraction was reduced (–30%for CETP and –11% for nTg mice). Castrated mice presented1.7-fold higher titers of anti-oxidized LDL (Ox-LDL) antibodiesthan sham-operated controls. Plasma levels of CETP, lipoproteinlipase, and hepatic lipase were not changed by castration. Kineticstudies showed no differences in VLDL secretion rate, VLDL-LDLconversion rate, or number of LDL and HDL receptors. Competitionexperiments showed lower affinity of LDL from castrated micefor tissue receptors. Diet-induced atherosclerosis studies showedthat testosterone deficiency increased by 100%, and CETP expressionreduced by 44%, the size of aortic lesion area in castratedmice. In summary, testosterone deficiency increased plasma levelsof apolipoprotein B-containing lipoproteins (apoB-LPs) and anti-OxLDLantibodies, decreased LDL receptor affinity, and doubled thesize of diet-induced atherosclerotic lesions. The expressionof CETP led to a milder increase of apoB-LPs and reduced atheroscleroticlesion size in testosterone-deficient mice.Supplementary key words low density lipoprotein receptor • lipoprotein lipase • lipolysis • plasma lipoprotein kinetics • oxidized low density lipoprotein • aortic atherosclerosis lesion • cholesteryl ester transfer protein
