Acta Physiologica 2011; Volume 202, Supplement 684
The Joint Conference (FAMÉ 2011) of the LXXVth Meeting of the Hungarian Physiological Society, XVIth Meeting of the Hungarian Society of Anatomists, Experimental Section of the Hungarian Society for Experimental and Clinical Pharmacology and Hungarian Society for Microcirculation and Vascular Biology
ROLE OF INFLAMMATION AND DYSREGULATION OF NRF2-DEPENDENT ANTIOXIDANT DEFENSE PATHWAYS IN VASCULAR AGING
Abstract number: L3
One of the major conceptual advances in our understanding of the pathogenesis of age-associated cardiovascular diseases has been the insight that aging per se promotes vascular inflammation even in the absence of traditional risk factors associated with atherogenesis (e.g. hyperhomocysteinemia, diabetes mellitus, hypertension or smoking). Recently the hypothesis has been put forward that multiple pro-inflammatory pathways converge on NF-kB (a master regulator of endothelial activation) in the aged arterial wall. There is an increasing amount of experimental data suggesting that activation of the local TNFa converting enzyme (TACE)-TNFa and the renin-angiotensin system, as well as an increased mitochondrial and NADPH oxidase derived production of reactive oxygen species (ROS), may underlie NF-kB induction and endothelial activation in aged arteries. Importantly, the transcriptional activity of NF-kB is modulated by evolutionarily conserved pathways involved in cellular redox homeostasis. Nrf2 is a transcription factor, which is activated by reactive oxygen species in the vasculature of young animals, leading to adaptive up-regulation of numerous ROS detoxifying and antioxidant genes. Our studies provide evidence that aging is associated with dysregulation of Nrf2 and, as a result, in aged organisms oxidative stress fails to activate Nrf2-regulated ROS detoxification systems in the vasculature. We propose that the impaired ability of vascular cells to mount an effective Nrf2-dependent antioxidant defense in response to age-related increases in ROS production contribute to NF-kB activation and vascular inflammation in aging. Thus, Nrf2 may provide a therapeutic target for countering oxidative stress associated with aging and thereby prevention of cardiovascular diseases in the elderly.
American Federation for Aging Research, the University of Oklahoma College of Medicine Alumni Association and the NIH (AG031085, AT006526, HL077256).
To cite this abstract, please use the following information:
Acta Physiologica 2011; Volume 202, Supplement 684 :L3