Effects of nitric oxide

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.

Key Words

• cardiovascular diseases;
• cell cycle;
• cell proliferation;
• diagnostic and therapeutic tools;
• imaging;
• nitric oxide;
• type 2 diabetes

Abbreviations and Acronyms

• BMC, bone marrow cell(s);
• cGMP, cyclic guanosine monophosphate;
• EGFR, epidermal growth factor receptor;
• eNOS, endothelial nitric oxide synthase;
• EPC, endothelial progenitor cell(s);
• GC, guanylate cyclase;
• NO, ;
• NOS, nitric oxide synthase;
• ROS, reactive oxygen species;
• T2DM, type 2 diabetes mellitus;
• VSMC, vascular smooth muscle cell(s)

Nitric oxide (NO) is a signaling molecule that regulates many functions, such as vascular tone, blood pressure, neurotransmission, immune response, and oxidation-sensitive mechanisms, , and . NO may act as an autocrine or paracrine messenger, and its production and degradation are cell type dependent. NO synthesis is catalyzed from L-arginine by a family of nitric oxide synthases (NOSs), varying from picomolar/nanomolar range for short periods to micromolar range for protracted periods . NO reacts with molecules such as oxygen, superoxide or metals, nucleic acids, and proteins. The major reactions involving NO support its rapid oxidation into nitrate and nitrite, which are now considered not inert end products but actors of a reverse pathway that represents an alternative source of NO when the endogenous L-arginine/NOS pathway is dysfunctional and .