[Pleiotrophic peroxisome induction by hypolipidemic agents in primates and rodents]

Hyperlipoproteinemia is the most important public health risk factor for ischemic heart disease and is still responsible for a high proportion of the annual deaths in Austria. Clofibrate and other structurally related compounds are hypolipidemic drugs used in the treatment of hyperlipoproteinemia. Peroxisome proliferators enhance peroxisomal enzyme activities and increase mRNA levels of the corresponding genes. Some of these effects may be mediated by peroxisome proliferator activated receptors (PPARs). Subchronic treatment of rodents with hypolipidemic drugs produces profound hepatomegaly and increases the incidence of hepatocellular carcinomas, which has not been found in primates. Up to now hypolipidemic drugs have been administered with caution in view of these results. In order to evaluate the interspecies differences in the regulation of the peroxisomal enzyme system we are establishing a cell model system.