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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, D. F. J. Ketelhuth, M. Gidlund and H. C. F. Oliveira^1,*

^* Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, Sao Paulo, Brazil
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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