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Leukocyte adhesion and its contribution on the local oxidative and nitrosative stresses in microcirculation
Author(s) -
Kar Saptarshi,
Kavdia Mahendra
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.590.16
Subject(s) - peroxynitrite , oxidative stress , nitric oxide , chemistry , adhesion , superoxide , inflammation , oxidative phosphorylation , cell adhesion molecule , microcirculation , biochemistry , biophysics , microbiology and biotechnology , immunology , biology , medicine , enzyme , organic chemistry
In diabetes, a number of adhesion molecules are over expressed leading to leukocyte adhesion and subsequent transmigration in the vessel wall. This is one of the early stages for vascular inflammation. These adherent or transmigrating leukocytes release high levels of nitric oxide (NO) and superoxide thereby increasing local oxidative and nitrosative stresses. In the current study, we developed a computational model to understand the effect of leukocyte adhesion and transmigration on the profiles of oxidative and nitrosative stress inducing free radicals NO, superoxide and peroxynitrite in a blood vessel. The results are presented for three cases: 1) A normal case with relatively low amount of leukocyte adhesion, 2) An oxidative stress case with leukocyte adhesion and transmigration and 3) A severe oxidative stress case with reduced SOD levels. The results indicate a significant increase in peroxynitrite concentration and decrease in NO concentration for the severe oxidative stress case with respect to the normal case. Decreasing NO formation could impair vasodilation whereas increasing peroxynitrite formation may initiate oxidation of sulfydryl groups in proteins and lipids and nitration of amino acids resulting in damage to the endothelial and smooth muscle cells of the blood vessel, which can contribute to the occurrence of cardiovascular related diseases. Supported by NIH R01 HL084337.