Atherosclerosis is enhanced by testosterone deficiency and attenuated by CETP expression in transgenic mice |
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Authors: | Casquero A C Berti J A Salerno A G Bighetti E J B Cazita P M Ketelhuth D F J Gidlund M Oliveira H C F |
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Institution: | Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, Sao Paulo, Brazil. |
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Abstract: | In this work, we investigated the impact of testosterone deficiency and cholesteryl ester transfer protein (CETP) expression on lipoprotein metabolism and diet-induced atherosclerosis. CETP transgenic mice and nontransgenic (nTg) littermates were studied 4 weeks after bilateral orchidectomy or sham operation. Castrated mice 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 presented 1.7-fold higher titers of anti-oxidized LDL (Ox-LDL) antibodies than sham-operated controls. Plasma levels of CETP, lipoprotein lipase, and hepatic lipase were not changed by castration. Kinetic studies showed no differences in VLDL secretion rate, VLDL-LDL conversion rate, or number of LDL and HDL receptors. Competition experiments showed lower affinity of LDL from castrated mice for tissue receptors. Diet-induced atherosclerosis studies showed that testosterone deficiency increased by 100%, and CETP expression reduced by 44%, the size of aortic lesion area in castrated mice. In summary, testosterone deficiency increased plasma levels of apolipoprotein B-containing lipoproteins (apoB-LPs) and anti-OxLDL antibodies, decreased LDL receptor affinity, and doubled the size of diet-induced atherosclerotic lesions. The expression of CETP led to a milder increase of apoB-LPs and reduced atherosclerotic lesion size in testosterone-deficient mice. |
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Keywords: | low density lipoprotein receptor lipoprotein lipase lipolysis plasma lipoprotein kinetics oxidized low density lipoprotein aortic atherosclerosis lesion cholesteryl ester transfer protein |
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