P340	Profiling of aortic smooth muscle cells gene expression during aging in rats.
1S.Nadaud, 1L.Monnet, 2J-B.Michel, 1S.Raoux, 3B.Corman, 1F.Soubrier
1INSERM U525, Paris, FR; 2INSERM U698, Paris, FR; 3Successaging, Paris, FR.

AIM: Aging is associated with impaired vascular function in both human and rodents. To investigate the mechanisms responsible for this vascular dysfunction, we studied gene expression modifications in aortic smooth muscle cells from young and old Wag/Rij rats. METHODS AND RESULTS: Aortic media of 2, 10 and 30 months-old female Wag/Rij rats were prepared, amplified, labeled and used for hybridization of Agilent rat oligonuleotide microarrays (20000 probes). Statistical analysis was performed using SAM (FDR=10%), hierarchical and K-means clustering. Gene expression variations were confirmed by real-time PCR. We observed that the number of modulated genes increases with age (59 between 2 and 10 months of age, 105 between 10 and 30 months and 276 between 2 and 30 months) with roughly as many genes induced and inhibited. These expression changes were confirmed by PCR on a selection of genes (85%). Most of the genes have their expression gradually increased or decreased during aging. However, some genes (20) only decrease after 10 months of age and some (20) are already decreased at 10 months of age and are not modified thereafter. We observed that a high number of these genes (around 40) are also modified and in the same direction during L-NAME-induced hypertension in rat aortic media. CONCLUSION: As it was previously hypothesized, we observe a concordant modification of gene expression profile between aging and hypertension, although the rats used do not develop a high blood pressure with age. Analysis of regulated genes will help understanding the factors implicated in vascular dysfunction during aging.

Copyright © 2005 S. Karger AG, Basel. Any further use of this abstract requires written permission from the publisher.