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, NO can exert opposite effects under diverse conditions. Indeed, several studies have indicated that low relative concentrations of NO seem to favor cell proliferation and antiapoptotic responses and higher levels of NO favor pathways inducing cell cycle arrest, mitochondria respiration, senescence, or apoptosis. Here we report the effects of NO on both promotion and inhibition of cell proliferation, in particular in regard to 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 cyclic guanosine monophosphate-dependent and -independent pathways. This growing field may lead to broad and novel targeted therapies against cardiovascular diseases, especially concomitant type 2 diabetes, as well as novel bioimaging NO-based diagnostic tools.