First 11 pages of thesis. - OPUS - Universität Würzburg

dependent relaxations using SOD and antioxidants 50, 51 . Further, deficiency of
vascular SOD results in impaired endothelial functions 47 . In addition to reducing
the bioavailability of nitric oxide, superoxide generation may also promote
endothelial cell apoptosis 52 .
Superoxide generation causes platelet adhesion and aggregation 53 .
NADPH oxidase mediated superoxide production causes increased
leukocyte/endothelial cell interaction in hypercholesterolemic mice 54 . Further,
SOD inhibits the expression of vascular cell adhesion molecule-1 (VCAM-1) and
intercellular cell adhesion molecule-1 (ICAM-1) in endothelial cells 55 , suggesting
that superoxide modulates the expression of adhesion molecules. Additionally,
superoxide promotes vascular smooth muscle cell migration and proliferation 52 .
Both superoxide and hydroxyl radical contribute to LDL-oxidation which induces
cholesterol accumulation in macrophages and leads to foam cell formation 56, 57 .
Ox-LDL acts as a chemotactic factor for monocytes and T-cells, the
predominant population of blood cells found in the atherosclerotic lesions.
1.3.3 Functional role of nitric oxide in atherosclerosis
Nitric oxide, named the ‘molecule of the year in 1992’ is an important cell
signaling, effector and vasodilator molecule with potentially strong
antiatherogenic actions. Of all its functions, it’s role as endothelium dependent
relaxing factor (EDFR) is the most recognized one, thought to reflect vascular
homeostasis. Nitric oxide mediates vascular smooth muscle cell relaxation by a
calcium-ion channel mediated activation of the cyclic guanosine
monophosphate (cGMP) pathway. Further, nitric oxide inhibits smooth cell
proliferation, leukocyte/endothelial cell interactions and platelet aggregation.
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