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Replacement of the ceil loss occurring after acute myocardial infarction has been proposed as a potential treatment to prevent heart remodeling and failure. On account that cardiomyocytes express VEGF receptors and that VEGF triggers mitogen-activated protein kinases, we investigated if VEGF gene transfer may induce cardiomyocyte replication. In a pig model of chronic myocardial ischemia achieved by Ameroid occlusion of the left circumflex coronary artery, we observed that direct intramyocardial injection of a plasmid encoding human VEGF[sub 165] induced a several-fold increase in cardiomyocyte mitotic index and in the number of cardiomyocyte nuclei per unit volume as compared with pigs receiving plasmid devoid of gene. Despite images of conventional cytokinesis were not observed, the fact that caryokinesis is an obligatory step for cell division suggests that our finding may contribute to the issue of heart regeneration and may potentially widen the therapeutic spectrum of VEGF gene transfer. [ABSTRACT FROM AUTHOR]

Clinical data suggest that the individual susceptibility to atherosclerosis is not accounted for only by exposure to classical or "emerging" vascular risk factors. Although recent investigations with transgenic animals have revealed new genetic determinants of susceptibility, little is known concerning this situation in human beings. Even though the human genome project might uncover specific genetic markers in the future, the only early and objective method to identify the susceptible individual at present is to detect atherosclerosis non-invasively. High resolution B-mode ultrasonography of superficial arteries coupled with advanced computer-assisted image processing systems is a highly reproducible method to perform a quali-quantitative early evaluation of already developed wall lesions. Clinically more significant, the detection of silent atherosclerosis has an additional value for risk factor assessment in the prediction of global vascular risk, a relevant index for decision-making in cardiovascular prevention. It is conceivable that the introduction of non-invasive measures of the atherosclerotic burden in risk stratification of asymptomatic subjects will help to target interventions for more rational risk factor control and to reduce the cost/benefit ratio of primary prevention.

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.

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.