First 11 pages of thesis. - OPUS - Universität Würzburg

transport pathway and is an essential ligand for the uptake and clearance of
atherogenic lipoproteins 138 . ApoE is a constituent of chylomicrons, very low
density lipoproteins (VLDL) and HDL. Genetic deletion of apoE in mice, a
species normally resistant to atherosclerosis, is associated with 4-5 times
increased plasma cholesterol levels. Although the pathomechanism of
atherosclerosis development differs from common human disease, the apoE ko
model has substantially shaped our understanding of the role of apoE in lipid
transport and proved to be a valid atherosclerosis model 139 .
1.6 Role of NOS isoforms in cardiovascular diseases
1.6.1 Role of eNOS in cardiovascular diseases
Endothelium derived nitric oxide plays a major role in modulating several
cardiovascular functions 140 . Nitric oxide generated by eNOS serves as an
endothelium derived relaxing factor, regulates vascular tone and blood
pressure. Furthermore, it exerts potential anti atherosclerotic effects as it
inhibits vascular smooth muscle cell proliferation, platelet aggregation and
leukocyte adhesion 140 , 141 . The importance of endothelium derived nitric oxide in
maintaining normal endothelial function has been described in detail in section
(1.3.3). Reduced bioavailability of nitric oxide has been associated with several
cardiovascular diseases. One of the potential mechanisms leading to reduced
nitric oxide bioavailability is the uncoupling of eNOS. Uncoupling of eNOS is
observed in several cardiovascular diseases but may also serve as an
important defense mechanism of the normal endothelium 142 . Furthermore,
alteration in the sub cellular localization of eNOS resulting in decreased activity
of the enzyme has been observed during various disease conditions 143 .
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