Effects of nitric oxide on cell proliferation: novel insights.

Nitric oxide (NO) has been suggested to be a pathophysiological modulator of cell proliferation, cell cycle arrest and apoptosis. In this context, opposite effects can be exerted by NO under diverse conditions. Indeed, several studies have indicated that low relative concentrations of NO seem to favour cell proliferation and anti-apoptotic responses whereas higher levels of NO favour pathways inducing cell cycle arrest, mitochondria respiration, senescence or apoptosis. Here, we report the NO effects on both promotion and inhibition of cell proliferation with particular concern on cardiovascular disease, diabetes and stem cells. Moreover, we focus on molecular mechanisms of action involved in the control of cell cycle progression, which include both cGMP-dependent and -independent pathways. This growing field may lead to broad and novel targeted therapies against cardiovascular diseases especially during concomitant type 2 diabetes, as well as novel bioimaging NO-based diagnostic tools.