Modulating endothelial nitric oxide synthase: a new cardiovascular therapeutic strategy

Zhang Y, Janssens SP, Wingler K, Schmidt HH, Moens AL. Modulating endothelial nitric oxide synthase: a new cardiovascular therapeutic strategy. Am J Physiol Heart Circ Physiol 301: H634-H646, 2011. First published May 27, 2011; doi:10.1152/ajpheart.01315.2010.-The pathogenesis of many cardiovascular diseases is associated with reduced nitric oxide (NO) bioavailability and/or increased endothelial NO synthase (eNOS)-dependent superoxide formation. These findings support that restoring and conserving adequate NO signaling in the heart and blood vessels is a promising therapeutic intervention. In particular, modulating eNOS, e. g., through increasing the bioavailability of its substrate and cofactors, enhancing its transcription, and interfering with other modulators of eNOS pathway, such as netrin-1, has a high potential for effective treatments of cardiovascular diseases. This review provides an overview of the possibilities for modulating eNOS and how this may be translated to the clinic in addition to describing the genetic models used to study eNOS modulation.