Marked neointimal lipoprotein lipase increase in distinct models of proclivity to atherosclerosis: a feature independent of endothelial layer integrity.

Lipoprotein lipase (LPL) in the arterial wall has been proposed to enhance the retention of apoB-containing lipoproteins, an early event in atherosclerosis. As the neointima is considered the primary site of lipid accumulation in atherogenesis, the arterial expression and location of LPL was investigated in distinct experimental models of neointimal formation in normolipidemic rabbits and rats. Neointima elicited by balloon aortic denudation or raised beneath an anatomically intact endothelial layer by placing a silastic collar around the common carotid artery, both showed a striking LPL immunostaining that mostly co-localized with neointimal smooth muscle cells. Besides, increased LPL protein and mRNA in deendothelialized aortas was demonstrated by Western and Northern blot analysis, respectively, suggesting an enhanced expression of LPL in injured arteries. It was concluded that LPL is increased in neointima developed in either denuded vessels or arteries with a preserved endothelium, a finding which suggests that LPL abundance may be an attribute of the neointima, whatever the stimulus that promotes its formation. On the basis of former evidence concerning the role of LPL in lipid retention, this study provides a possible explanation for the injury-induced vessel susceptibility to atherosclerosis, and the particular proneness of the neointimal layer to lipid accretion.

Determination of bezafibrate, ciprofibrate and fenofibric acid in human plasma by high-performance liquid chromatography.

A selective high-performance liquid chromatographic method to assess either bezafibrate, ciprofibrate or fenofibric acid plasma levels is described. Drugs are extracted with diethyl ether, after acidification with HCL. An isocratic acetonitrile 0.02 M H3PO4 (55:45) mobile phase, a C18 microns) column and UV detection are used. The LOQ found was 0.25 microgram/ml for the three fibrates. Intra- and inter-assay accuracy ranges were 90-107% and 82-111%: 96-115% and 94-107%: 94-114% and 94-126% for bezafibrate, ciprofibrate and fenofibric acid, respectively. Intra- and inter-assay precision (C.V.% ranges) were 1.72-3.06% and 2.66-7.67%: 1.88-4.64% and 0.62-2.99%: 1.26-4.69% and 3.56-7.17% for the three fibrates studied. Its sensitivity, accuracy and precision make it a useful tool for monitoring plasma levels of these drugs in a clinical setting and for research purposes.

Injury produces early rise in lipoprotein lipase activity in rabbit aorta.

The mechanisms following intimal injury predisposing towards atherosclerotic changes have not been fully elucidated. We speculated that a local increase in the enzyme lipoprotein lipase (LPL) might explain a higher susceptibility of the damaged intima to lipid accretion, and so we investigated the effect of balloon endothelial denudation on LPL activity and cholesterol content (LPLa and Cholc, respectively), in aortas from normolipidemic male New Zealand white rabbits. Arteries were obtained from injured and control animals after 2, 6, 8 and 10 weeks to evaluate the shortest period after de-endothelialization necessary to detect LPLa changes. Injury resulted in a 4-fold LPLa rise (P < 0.01), as early as 2 weeks, and the enzymatic activity remained increased throughout the study period. A mild but significant 22% Cholc increase (P < 0.03) was found after 2 weeks of injury, even in this normolipidemic rabbit model. We conclude that physical damage to the intima markedly and soon increases LPLa. This finding might account for the higher lipid accumulation by injured vessels, providing additional support to the hypothesis of LPL as an atherogenic mediator.

[Repeatability of insulin sensitivity estimation using the Minimal Model and comparison with a modified short low-dose insulin tolerance test]. / Reproducibilidad de la cuantificación de la sensibilidad a la acción insulínica con el modelo mínimo y comparación con un test de tolerancia a bajas dosis de insulina.

Hyperinsulinemia and insulin-resistance are metabolic disturbances associated with obesity, essential hypertension, hypertriglyceridemia, glucose intolerance, overt non-insulin dependent diabetes mellitus, polymetabolic syndrome and atherosclerotic disease. The assessment of in vivo insulin sensitivity (SAI in vivo) changes achieved by life style modifications or drug interventions require a reproducible technique. To evaluate the day-to-day intra-individual repeatability of SAI-in vivo, we determined the variation in the SI index (calculated from the Minimal Model of Bergman modified by insulin or MMins) in 11 subjects with a wide range of insulin-resistance. SI (first study) varied from 0.82 to 8.48 x 10(-4) min-1/microU.mL (4.43 +/- 2.85 x 10(-4) min-1/microU.mL mean +/- SD) and highly correlated with SI (second study) (r = 0.89; p = 0.0002). The average interday coefficient of variation was 20.9 +/- 13.9% and was similar in subjects with low or high SI values. We also measured SAI in vivo by assessing the rate of serum glucose decline induced by human cristalline insulin 0.025 U/kg IV dose after a 12-14 hours fasting period (a modified Bonora's method or BBD) in 11 subjects. No subject presented biochemical or symptomatic hypoglycemia. SAI in vivo values determined by BBD varied from 21 a 234 mumol/ml/min (134 +/- 64.8 mumol/ml/min, mean +/- SD). We found a highly significant correlation between SI values obtained from MMins and SAI in vivo assessed by the BBD (r = 0.89, p = 0.0002). Our results suggest that the Mmins is a fairly reproducible procedure and that a BBD is an acceptable option to quantify SAI in vivo, mainly when a fast-execution practice is necessary or cost restrictions are required.