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Originally published In Press as doi:10.1194/jlr.M600135-JLR200 on April 7, 2006

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Journal of Lipid Research, Vol. 47, 1526-1534, July 2006
Copyright © 2006 by American Society for Biochemistry and Molecular Biology

Atherosclerosis is enhanced by testosterone deficiency and attenuated by CETP expression in transgenic mice

A. C. Casquero*, J. A. Berti*, A. G. Salerno*, E. J. B. Bighetti*, P. M. Cazita{dagger}, D. F. J. Ketelhuth§, M. Gidlund§ and H. C. F. Oliveira1,*

* Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, Sao Paulo, Brazil
{dagger} Laboratório de Lípides (LIM-10), Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil
§ Departamento de Imunologia, Instituto de Ciências Biomédicas, Universidade de Sao Paulo, Sao Paulo, Brazil

Published, JLR Papers in Press, April 7, 2006.

1 To whom correspondence should be addressed. e-mail: ho98{at}unicamp.br

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.

Supplementary key words 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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