The effect of NO/EDRF and monocytes/macrophages on LDL-oxidation

Beside prostaglandin (PG) I2 and tissue plasminogen activator (tPA), nitric oxide (NO) is a key fepellant substance contributing to haemostatic balancing. The role of low-density lipoproteins (LDL) in the pathogenesis of atherosclerosis has been gaining increasing importance. It is well accepted that LDL in their modified (i.e. oxidized) form are no longer recognized by the LDL-receptor, but are taken up by cells of the arterial wall, especially macrophages, in a non-regulated manner through the so called scavenger-receptor pathway. This process leads to the formation of foam cells, the hallmark of the atherosclerotic lesion. NO is also produced in relevant amounts by macrophages. The interaction of NO and LDL with macrophages is thus of key importance in the onset of early lesions. While oxidized LDL (oxLDL) are resulting in a decreased NO availability, NO seems to prevent LDL-oxidation. In contrast, however, in the presence of superoxides oxidation may result. All these potential actions have to be discussed in view of the extremely short half-life of NO indicating that these actions are restricted most likely to the local site of biosynthesis being dependent on the actual concentration, the duration of availability and the presence of transition metals. These findings indicate that NO may play a dual pro- and antiatherosclerotic role being dependent on local factors only.