Nitric oxide and mechanisms of redox signalling: matrix and matrix-metabolizing enzymes as prime nitric oxide targets

One of the greatest biomedical breakthroughs of the twentieth century was t he discovery of endothelium-derived relaxing factor and its identification as nitric oxide (NO). NO has received special attention ever since: besides its potent vasodilatory and vasoprotective effects, NO was identified as a key player in innate immunity and was found to act as an unconventional ty e of neurotransmitter. This article. p focuses on mechanisms of NO signall ing that form the basis of functional cell responses to accommodate changes in the cellular microenvironment. Redox-based regulation of signal transdu ction and, on a more long-term scale, changes in gene expression will be ex emplified by NO-modulation of matrix components and matrix-metabolizing enz ymes. It seems to be a safe bet that ongoing analyses of NO signalling and gene expression will provide a wealth of promising therapeutic targets in h uman diseases. (C) 2001 Elsevier Science B.V. All rights reserved.