Abstract 267: Redox-Dependent Transcriptional Regulation: A Potential Mechanism for Collateral Growth Impairment During Chronic Oxidative Stress
Vascular risk factors characterized by oxidative stress are correlated with impaired collateral growth through mechanisms largely unknown. Spontaneously hypertensive rats (SHR) with increased oxidative stress were used to investigate potential mechanisms mediating impaired collateral compensation. Microarray analysis of global gene expression was performed with control and collateral mesenteric artery samples (n=4) from SHR and their normotensive controls (WKY) 24 hours after model creation. In SHR control arteries, several mechano-sensitive and redox-dependent transcription regulators were down-regulated including Jun (-5.2X, P=0.02), Egr-1 (-4.1X, P=0.01), and NFkB1 (-1.95X, P=0.04). Collateral arteries of WKY and SHR exhibited a fundamentally different gene expression pattern (<7% overlap), especially for molecules regulating cell growth and proliferation and gene expression. Predicted binding sites for NFkB and AP-1 were present in the genes altered in WKY but not SHR collaterals. Immunostaining demonstrated increased NFkB nuclear translocation in WKY but not in SHR collaterals (see figure). Increased NFkB nuclear translocation was also seen in collaterals of SHR pretreated with the anti-oxidant apocynin (Apo), which we have previously shown to restore a normal redox status and collateral growth. Based upon these results, we propose redox-dependent modulation of mechano-sensitive transcription factors as a mechanism to explain, at least in part, the fundamental differences in collateral gene expression between WKY and SHR and the impairment of collateral growth during chronic oxidative stress.
- © 2012 by American Heart Association, Inc.