Submitted on March 21, 2006
Accepted on April 7, 2006
Atherosclerosis is enhanced by testosterone deficiency and attenuated by cetp expression in transgenic mice
Andrea C. Casquero, Jairo A. Berti, Alessandro G. Salerno, Eliette J. B. Bighetti, Patrícia M. Cazita, Daniel F. J. B. Ketelhuth, Magnus Gidlund, and Helena C. F. Oliveira
Depto. de Fisiologia e Biofisica, Universidade Estadual de Campinas (UNICAMP), Campinas, Sao Paulo 13083-970
Corresponding Author: ho98{at}unicamp.br
In this work we investigated the impact of testosterone deficiency and CETP expression on lipoprotein metabolism and diet-induced atherosclerosis. CETP transgenic mice and non-transgenic (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, while the HDL fraction was reduced: -30% for CETP and -11% for nTg mice. Castrated mice presented 1.7 fold higher titers of antibodies anti-oxidized (ox) LDL 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 in the 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% while CETP expression reduced by 44% the size of aortic lesion areas in castrated mice. In summary, testosterone deficiency increased plasma levels of apoB-lipoproteins and antibodies anti-oxLDL, decreased LDL-receptor affinity and doubled the size of diet induced atherosclerotic lesions. The expression of CETP led to a milder elevation of apoB-lipoproteins and reduced atherosclerotic lesion size in testosterone deficient mice.
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