[Kinetic modeling of LDL oxidation using software (NELOP program) and validation in a population at vascular risk]

Oxidized LDL (low density lipoprotein) are considered to be the major initiating event in atherogenesis. In vitro models have been studied but no mathematic modeling can assess quantitatively the oxidability of LDL and antioxidant effects. We have developed a mathematic modeling allowing quantification of different kinetic parameters to LDL oxidation. This model has been validated by means of a software (software NELOP) in normal population (HV) and in a cardiovascular risk population, hemodialysis (HD). LDL are collected and purified by sequential ultracentrifugations from 12 healthy volunteers and hemodialysis patients. LDL oxidability (0.1 microM) is initiated by 5 microM copper and monitored continuously by conjugated diene production. All parameters are evaluated and correlated to those obtained by NELOP. Significant correlations between measured and calculated parameters (Vmax: r2 = 0.99, p < 0.05) allow to validate NELOP in both populations. Our results show that hemodialysis LDL present an enhanced susceptibility to copper induced oxidation (lag time: 96.6 +/- 48.6 mn in HV versus 54.5 +/- 22.2 mn in HD). NELOP seems to be a useful tool to evaluate LDL oxidation in cardiovascular risk populations.