Microarray analysis of strain and age‐specific gene expression associated with strain‐dependent impairment of flow‐induced collateralization in rat mesenteric arteries

Ability to compensate for arterial occlusion via collateralization (enlargement of pre‐existing bypass vessels) is impaired with advanced aging in humans. A previous study in our lab showed a profound impairment of flow‐induced collateralization (FIC) in the mesenteric arteries (MA) of Fisher344/Brown Norway F1 hybrid (F1) but not Brown Norway (BN) rats. The goal of this study was to identify the differentially expressed genes uniquely associated with differences in strain and FIC of 6, 15 or 24 mo old F1and BN MA. Microarray analysis was performed using the Affymetrix GeneChip Rat Expression Array 230A and the Ingenuity IPA software. A mean of 1524 genes (p<0.01) were found in each of the 9 comparisons between rat strain and age (max = 2908 genes in the 15 vs. 24 mo BN MA group, min =268 genes in the 6 vs. 15 mo F1 MA group). When comparing the 4550 genes associated with transition of MA from 6, 15 and 24 mo in both strains, 25 genes were downregulated at 24 mo in the F1 and upregulated in the BN rats more than 2‐fold. In particular, kallikrein B (KLKB1), a growth factor previously shown to rescue impaired angiogenesis during ischemic revascularization was downregulated 67‐fold in F1 and upregulated 79‐fold in the BN rats at 24 vs. 15 mo. In conclusion, our results suggest that the age‐related FIC impairment is correlated with downregulation of a large number of genes including kallikrein B. Support: AG022691.