Age-dependent increase of NF-kappaB translocation and PDGF-B expression in aortic endothelial cells of hypercholesterolemic rats.

The objective of this study was to determine whether there was an age-dependent difference in promoting nuclear translocation of NF-kappa B and platelet derived growth factor expression in aortic endothelial cells between two groups of Wistar rats of 2 and 10 months in age, respectively, accompanied by hypercholesterolemia. The serum cholesterol levels became significantly higher in the older rats after taking a cholesterol-enriched diet for 16 weeks (129.3+/-11.9 vs. 194.5+/-22.6 mg/dl, P<0.01). The increase in total cholesterol levels were due to an elevation of LDL cholesterol since serum HDL cholesterol concentrations were similar in rats on either a high cholesterol- or a standard diet. Immunohistologic staining revealed nuclear translocation of NF-kappaB in aortic endothelial cells of rats was responsible for a high cholesterol uptake by cells. PDGF-B production was also increased in the endothelial cells of these animals as identified by situ hybridization and immunohistologic staining. Interestingly, the intensity of PDGF-B expression in the 10 months old rats was markedly higher than those of 2 months old. Taken together, these findings provide evidence that there was an elevation of serum cholesterol levels coinciding with an increase of PDGF-B expression in older rats, in which NF-kappaB might be an important transcription factor in mediating a hypercholesterolemia-induced PDGF-B expression.