title: Atherosclerosis is enhanced by testosterone deficiency and attenuated by CETP expression in transgenic mice.
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.
authors.affiliation: Departamento de Fisiologia e Biofísica, Instituto de Biologia, Universidade Estadual de Campinas, Sao Paulo, Brazil.
authors.forename: A C
authors.initials: AC
authors.lastname: Casquero
authors.forename: J A
authors.initials: JA
authors.lastname: Berti
authors.forename: A G
authors.initials: AG
authors.lastname: Salerno
authors.forename: E J B
authors.initials: EJ
authors.lastname: Bighetti
authors.forename: P M
authors.initials: PM
authors.lastname: Cazita
authors.forename: D F J
authors.initials: DF
authors.lastname: Ketelhuth
authors.forename: M
authors.initials: M
authors.lastname: Gidlund
authors.forename: H C F
authors.initials: HC
authors.lastname: Oliveira
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000209:etiology* / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism; D053480:Cholesterol Ester Transfer Proteins; D004036:Diet, Atherogenic; D015870:Gene Expression; D006023:Glycoproteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009919:Orchiectomy; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D013739:Testosterone / Q000172:deficiency*
chemical_list: C506642:CETP protein, human; D002352:Carrier Proteins; D053480:Cholesterol Ester Transfer Proteins; D006023:Glycoproteins; D008055:Lipids; D008074:Lipoproteins; D011994:Recombinant Proteins; D013739:Testosterone