Functional significance of hsp90 complexes with NOS and sGC in endothelial cells

Although the existence of hsp90-NOS and hsp90-sGC complexes is now firmly established, their role in many pathophysiological processes remain unclear. These complexes may represent physiological mechanisms aimed at maximizing intracellular cGMP production in response to endogenous or drug-derived NO in endothelial cells and thus affecting permeability, proliferation, migration and apoptosis. Along with minimizing NO scavenging by superoxide and reducing the formation of peroxynitrite, these complexes may also prolong sGC stability by retarding its degradation. Our work and that of others have demonstrated that, depending on the environment, sGC interaction with hsp90 can optimize sGC enzyme activity or modulate sGC survival. This review addresses the functional significance of hsp90 complexes with NOS (eNOS, iNOS) and sGC in endothelial cells relevant for maintaining endothelial barrier integrity and angiogenesis. Structural and functional characteristics of sGC, its expression, transcriptional and post-translational regulation, as they relate to sGC-hsp90 interactions, will also be examined.