Abnormal Shear‐mediated Gene Expression in Mesenteric Arteries of the Spontaneously Hypertensive Rat Explains Reduced Capacity for Collateral Growth

Analysis of global gene expression in mesenteric control and high flow collateral arteries was used to investigate potential mechanisms responsible for impaired collateral growth in the Spontaneously Hypertensive rat (SHR), an animal model of essential hypertension with vascular redox and metabolic abnormalities. Control and collateral arteries were harvested 24 hours after arterial ligation, RNA was isolated and microarray analysis performed. Comparison of collaterals to same animal controls indicated 214 genes with altered expression (P<0.05); with only 14 common between SHR and the normotensive controls (WKY). Ingenuity Pathways Analysis revealed fundamental differences in important functional categories (see table). Identification of transcription factor binding sites with a motif modeler program predicted a major difference in transcription factors mediating gene expression. This included a role for the redox and shear stress sensitive nuclear factor kappa B and nuclear factor activator protein‐1 in WKY but not SHR collaterals. Together with our previous studies, the results suggest that a fundamental abnormality in shear‐mediated gene expression, presumably due to chronic oxidative stress, mediates the reduced capacity for collateral growth in the SHR.