RESUMEN
BACKGROUND: The antiatherogenic role of different HDL subclasses is still controversial. HDL particles of the same size can have different lipid contents in some physiopathological situations. However, little is known about the plasma lipid levels of HDL subclasses when they are separated by their hydrodynamic diameter. METHODS: Triglycerides (Tg), phosphatidylcholine (Ph), and cholesterol (C) plasma concentrations of HDL subclasses, were determined by enzymatic staining on polyacrylamide gradient gel (PAGE) in 50 pediatric patients with metabolic syndrome (MS), and 50 control children paired by age and gender. Proteins of HDL subclasses were also stained for the assessment of the relative size distribution of HDL. RESULTS: Relative HDL size distribution was shifted to small particles in MS pediatric patients when determined per protein. In contrast, cholesterol plasma concentrations corresponding to the HDL2b, 2a, 3a, and 3b subclasses were decreased; triglycerides of HDL3b and 3c, as well as plasma phospholipids from HDL3c, were elevated in MS patients as compared to controls. The C-to-Ph ratio, considered as indicative of HDL composition, was similar among the 5 HDL subclasses in control subjects, whereas this ratio gradually decreased from large HDL2b to small HDL3c in the MS group. Cholesterol plasma concentrations of HDL subclasses correlated with the components of the MS. CONCLUSIONS: Lipids of HDL subclasses provide more and accurate information than the relative HDL size distribution determined by protein staining, and may contribute to understand better HDL metabolism and the coronary risk associated to these lipoproteins.
Asunto(s)
Electroforesis en Gel de Poliacrilamida/métodos , Enzimas/metabolismo , Lipoproteínas HDL/sangre , Lipoproteínas HDL/aislamiento & purificación , Síndrome Metabólico/sangre , Estudios de Casos y Controles , Niño , Colesterol/sangre , Femenino , Humanos , Masculino , Fosfatidilcolinas/sangre , Propiedades de Superficie , Triglicéridos/sangreRESUMEN
Changes in aortic vasoreactivity during the postnatal pancreatic critical window, where insulin and glucose, which modify vasoreactivity, are elevated, were studied and compared to those in control and metabolic syndrome (MS) rats. Twelve 21- and 28-day-old rats were used. To develop MS rats, male Wistar animals were given 30% sucrose in drinking water since weaning and used when 6 months old. Glucose and insulin levels were higher during suckling and decreased after weaning, and insulin and triglycerides levels increased in MS rats. Contraction elicited by norepinephrine (NE) was stronger than KCl contraction at all ages. KCl-induced contraction increased with, age being stronger in control rats; it further increased in MS rats. Norepinephrine-induced contraction increased from day 12 to day 28 but stabilized from day 21 to day 28; it was stronger in controls and increased in MS rats. Vasorelaxation to acetylcholine in NE precontracted rings did not change during the neonatal period, being similar to MS rats and lower than in controls. Insulin-induced increase in contraction elicited by KCl increased from day 12 to day 28 and increased from control to MS rats. There is a postnatal critical window in vasoreactivity that might predispose to cardiovascular diseases in adults.
Asunto(s)
Aorta/fisiopatología , Glucemia/metabolismo , Enfermedades Cardiovasculares/etiología , Insulina/sangre , Síndrome Metabólico/fisiopatología , Páncreas/metabolismo , Vasoconstricción , Vasodilatación , Factores de Edad , Animales , Animales Recién Nacidos , Aorta/efectos de los fármacos , Peso Corporal , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/fisiopatología , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Masculino , Síndrome Metabólico/sangre , Síndrome Metabólico/complicaciones , Páncreas/crecimiento & desarrollo , Ratas , Ratas Wistar , Sacarosa , Vasoconstricción/efectos de los fármacos , Vasoconstrictores/farmacología , Vasodilatación/efectos de los fármacos , Vasodilatadores/farmacologíaRESUMEN
BACKGROUND: Rosiglitazone is an agonist of the peroxisome proliferator-activated receptor (PPAR) gamma that may modify HDL metabolism in humans, but this effect has not been completely elucidated. Therefore, we determined the effect of rosiglitazone on apo AI turnover, HDL structure, and PON1 plasma activity. METHODS: Kinetic studies of HDL-apo AI radiolabeled with (125)I were performed in 7 chow-fed, male, New Zealand white rabbits after 6 weeks of 0.32 mg/kg/d rosiglitazone-treatment vs. vehicle-treated rabbits (n=11). HDL size distribution was determined by polyacrylamide gradient electrophoresis and paraoxonase-1 (PON1); plasma activity was assessed spectrophotometrically using phenylacetate as substrate. RESULTS: Fractional catabolic rate (FCR) of HDL apo AI was higher in the rosiglitazone-treated group than in the control group (0.031+/-0.004 vs. 0.025+/-0.006 pools/h, respectively, p<0.05). The mean apo AI production rate (PR) was 62% higher in the rosiglitazone group as compared to controls (0.918+/-0.238 vs. 0.564+/-0.160 mg/kg/h, p<0.01). Accordingly, apo AI plasma levels in rosiglitazone-treated animals were about 37% higher than in the control group. Rosiglitazone-induced changes in apo AI turnover appeared concomitantly with a significant increase of phospholipids and a decrease in colesteryl esters content of the HDL. Compositional changes resulted in a relative increase of the HDL3b and HDL3c subfractions and a significant enhancement of the plasma PON1 activity (488.5+/-138.2 vs. 595.2+/-179.4 micromol/min/ml, p<0.05). CONCLUSIONS: Rosiglitazone increased apo AI plasma concentrations, resulting from an enhancement of apo AI synthesis, and induced the synthesis of smaller HDL particles with a concomitant increase of plasma PON1 activity. These modifications may contribute to the anti-atherogenic potential of rosiglitazone.