RESUMEN
Adult male Sprague-Dawley rats were hypophysectomized and connected to an automatic i.v. infusion system. The same daily dose of human GH (hGH) was given either as eight daily pulses (3-h intervals) to mimic the male specific secretory pattern of GH or as a continuous infusion of GH, to mimic the female secretory pattern. Hypophysectomized rats received i.v. replacement therapy with L-thyroxine and cortisol. The rats were treated for 5 days. The serum cholesterol concentration was higher when hGH was given continuously than when hGH was given as eight daily pulses. The concentration of high-density lipoprotein (HDL)-cholesterol was not influenced by intermittent GH treatment, but increased when hGH was given as a continuous infusion. The serum concentration of apolipoprotein (Apo) E increased following treatment with a continuous infusion of hGH, whereas eight daily pulses of hGH had no effect. The serum concentration of ApoA-I was unaffected by hGH treatment. The serum concentration of ApoB decreased to the same degree whether hGH was given as a continuous infusion or as eight daily pulses. The serum concentration of triglycerides was not affected by hGH treatment. These results indicate that the higher serum HDL-cholesterol and serum ApoE concentrations of female rats may be due to their more continuous secretion of GH. In contrast, the effects of GH on the serum concentration of ApoB, which is not sexually differentiated, may be independent of the mode of GH secretion.
Asunto(s)
Apolipoproteínas E/sangre , Colesterol/sangre , Hormona del Crecimiento/metabolismo , Animales , Apolipoproteínas B/sangre , HDL-Colesterol/sangre , Metabolismo Energético/efectos de los fármacos , Hormona del Crecimiento/administración & dosificación , Hormona del Crecimiento/farmacología , Hidrocortisona/farmacología , Hipofisectomía , Masculino , Ratas , Ratas Endogámicas , Tasa de Secreción/fisiología , Caracteres Sexuales , Tiroxina/farmacología , Aumento de Peso/efectos de los fármacosRESUMEN
Antibodies against oxidized low density lipoproteins (Ox-LDLs) have been proposed to be independent predictors of atherosclerosis development. The main aims of the current study were to (1) compare antibody titers to Ox-LDL in patients with heterozygous familial hypercholesterolemia (n=51) with those in matched controls (n=45) and (2) analyze whether the antibody titers were related to the extent of atherosclerosis, as assessed cross-sectionally and prospectively by ultrasonography in the 2 study groups. Antibody titers were determined with a solid-phase ELISA, and plates were coated with the antigens Ox-LDL or malondialdehyde-treated LDL (MDA-LDL) as well as with the postcoat only (5% dry milk powder). Antibody titers were expressed as absorbance [(value in patient serum minus that in postcoat) divided by (Internal Standard Serum minus postcoat)]. There were no significant differences in antibody titers against Ox-LDL or MDA-LDL between the group of patients with familial hypercholesterolemia and the controls. In cross-sectional comparisons, no significant associations were observed between the intima-media thickness of the carotid or femoral arteries and antibody titers against Ox-LDL or between plaque occurrence and these titers. Patients with a history of myocardial infarction had significantly lower IgM titers against Ox-LDL compared with patients without a history of myocardial infarction and with controls. In conclusion, mean values for antibody titers against Ox-LDL were not increased in the patient group compared with a healthy control group, and no positive, significant relationship was observed between antibody titers and the extent of atherosclerosis, as measured by ultrasound, in the carotid or femoral arteries. Taken together, these findings indicate that the relationship between the autoimmune response to Ox-LDL and the extent of atherosclerosis is more complex than previously anticipated.