THE EFFECT OF NO EDRF AND MONOCYTES MACROPHAGES ON LDL-OXIDATION

Beside prostaglandin (PG) I-2 and tissue plasminogen activator (tPA), nitric oxide (NO) is a key repellant substance contributing to haemost atic balancing. The role of low-density lipoproteins (LDL) in the path ogenesis 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 t o the formation of foam cells, the hallmark of the atherosclerotic les ion. NO is also produced in relevant amounts by macrophages. The inter action of NO and LDL with macrophages is thus of key importance in the onset of aerly lesions. While oxidized LDL (oxLDL) are resulting in a decreased NO availability, NO seems to prevent LDL-oxidation. In cont rast, however, in the presence of superoxides oxidation may result. Al l these potential actions have to be discussed in view of the extremel y short half-life of NO indicating that these actions are restricted m ost likely to the local site of biosynthesis being dependent on the ac tual concentration, the duration of availability and the presence of t ransition metals. These findings indicate that NO may play a dual pro- and antiatherosclerotic role being dependent on local factors only.