Clinical & Experimental Cardiology
Open Access

A probable protective mechanism for NO/cGMP/G-kinase activity is to raise Nrf2 activity

5^th International Conference on Clinical & Experimental Cardiology

April 27-29, 2015 Philadelphia, USA

Martin L Pall

Posters-Accepted Abstracts: J Clin Exp Cardiolog

Abstract :

Although insufficient bioavailability of NO is not the cause of cardiovascular disease (Int J Mol Sci 2013 Nov 13;14(11):22274-330.), NO signaling through cGMP and G-kinase is protective; the question is how does it work? It is the author?s view that the primary mechanism of action of this signaling pathway is likely to be that it raises Nrf2 activity. Protein kinase G has been shown to raise Nrf2 activity, a very important cytoprotective mechanism known to be raised by numerous health promoting factors. Nrf2 is a transcription factor that acts to raise the levels of many different enzymes with antioxidant activities and also lower inflammatory responses while raising levels of enzymes of energy metabolism and stimulating mitochondrial biogenesis. It also acts to raise autophagy, increasing degradation of toxic protein aggregates and dysfunctional organelles. The autophagy response is useful in lowering tissue remodeling, as is another response to Nrf2, stimulation of dedifferentiation fibroblasts, thus lowering fibrosis. It should not be surprising, given the common role of oxidative stress; chronic inflammation and mitochondrial dysfunction in various chronic inflammatory diseases that Nrf2 helps prevent and/or treat a large number of such diseases including the including atherosclerosis, ischemic cardiovascular disease, vascular endothelial dysfunction and heart failure, at least in animal model studies. In conclusion, it is likely that raising Nrf2 is an important mechanism by which the NO/cGMP/G-kinase signaling pathway can help prevent or treat various types of cardiovascular disease. Nrf2 may well play a similar role in a variety of NO/ONOO(-) cycle diseases. Citation: Pall ML and Levine S. Nrf2 regulator of detoxification, antioxidant, antiinflammatory and cytoprotection is raised by health promoting factors. Acta Physiologica Sinica, in press.