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First 11 pages of thesis. - OPUS - Universität Würzburg

First 11 pages of thesis. - OPUS - Universität Würzburg

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ate at which superoxide is degraded by SOD (2x10 9 M -1 sec -1 ). Further<br />

dismutation <strong>of</strong> superoxide by SOD can occur only if the latter enzyme is present<br />

in the same compartment in which superoxide is produced. In addition to being<br />

a significant source <strong>of</strong> eNOS mediated nitric oxide production, the endothelium<br />

is also a significant source <strong>of</strong> superoxide production in atherosclerotic vessels 70 .<br />

Since under these conditioms nitric oxide and superoxide are produced in the<br />

same cellular compartment, i.e., the endothelial cell, they can immediately react<br />

to form peroxynitrite. Peroxynitrite is a strong oxidant which alters the function<br />

<strong>of</strong> biomolecules by protein nitration and lipid peroxidation 71 with secondary<br />

tissue injury 39, 40 . Subintimal lipoprotein oxidation by peroxynitrite may initiate<br />

the formation <strong>of</strong> fatty streaks and subsequent plaque development 39 .<br />

Peroxynitrite may also contribute to endothelial cell dependant vascular<br />

oxidation.<br />

Figure 3: Proposed functional role <strong>of</strong> nitric oxide and superoxide in normal and atherogenic<br />

conditions, respectively.<br />

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