Role of nitric oxide in the control of apoptosis in the microvasculature.

Cell death occurs by either apoptosis or necrosis. Apoptosis is a cellular event in which a sequence of biochemical and morphological changes conclude in the death of the cell. Apoptosis is an important mechanism to control the number of cells and maintain tissue architecture. Nitric oxide (NO) is a multifunctional molecule that is synthesized by a family of enzymes, namely nitric oxide synthases (NOS). NO is implicated in several physiological functions within the microvascular environment, i.e. regulation of vascular tone, antiplatelet and antileukocyte properties and modulation of cell growth. Several investigations have demonstrated effects of NO on gene transcription. In this regard, NO has been also implicated in the apoptotic processes. The goal of the present review is to summarize the current knowledge about the relationship between NO and different genes involved in the apoptotic phenomena with focus in the cells of the microvascular environment, i.e. monocytes/macrophages, endothelium and vascular smooth muscle cells. Different studies have revealed that stimulation and inhibition of different genes are required to stimulate apoptosis. NO modulates the expression of bcl-2 family members, p53, interleukin-1 beta-converting enzyme family proteases and the cytokine receptor Fas. Therefore, NO generated from NO donors or synthesized by NOS induces cell death via apoptosis in a variety of different cell types. On the other hand, in the endothelial cells NO seems to have a relevant role in the maintenance of the confluent endothelial monolayer inhibiting apoptotic-related mechanisms. Furthermore, the redox states of the cells play an important role in the effects of NO as promotor of apoptosis. There have been exciting advances in the understanding of the molecular relationship between apoptosis and NO. Therefore, NO could be an important mediator to consider in the context of future therapeutic applications particularly considering apoptosis as a mechanism to maintain vascular architecture.