Microarray analysis of strain and age‐specific gene expression associated with age‐dependent intimal thickening of rat thoracic aorta

Age‐related structural vascular changes such as intimal and medial layer thickening may predispose humans to cardiovascular disease. The goal of the study was to identify the differentially expressed genes associated with age‐related vascular pathology in the thoracic aortas (TA) of 6, 15 and 24 mo old Fisher344/Brown Norway F1 hybrid (F1) and Brown Norway (BN) rats. The morphometric analysis showed that F1 TA had significantly increased intimal layer thickening at 24 vs. 6 mo, whereas BN TA showed only minimal medial and intimal thickening. The microarray analysis was performed using the Affymetrix GeneChip Rat Expression Array 230A and the Ingenuity IPA software. A mean of 1459 genes (p<0.01) were found in each of the 9 comparisons between rat strain and age (max = 3628 genes in the 24 mo F1 vs. BN TA group, min =135 genes in the 6 vs. 15 mo F1 TA group). When comparing the top 10 canonical pathways in F1 vs. BN strain at 6 and 24 mo, the NRF‐2 mediated oxidative stress response pathway contains 10 genes specific to the F1, and 17 genes specific to the BN strain. Among those, superoxide dismutase 3 (SOD3) is downregulated at 24 mo only in F1 rats, which suggests a role of reactive oxygen species in intimal remodeling. In conclusion, age‐associated vascular remodeling is correlated with differentially expressed molecules and molecular pathways due to differences in both age and genetic background. Support: AG022691.