Computational model for oxidative and nitrosative stress for endothelial dysfunction related leukocyte adhesion and transmigration

Endothelial dysfunction is characterized by increased superoxide production in endothelial cells causing them to overexpress adhesion molecules. This leads to leukocytes present in the lumen to roll along the endothelial region. The rolling of leukocytes promotes diffusion of free radicals into the leukocytes, increasing the expression of adhesion molecules on the leukocyte. Increased expression of adhesion molecules in both leukocytes and endothelial cells promotes binding of leukocytes to the endothelium. Earlier studies have shown that endothelial leukocyte adhesion triggers the respiratory burst of free radical species from the leukocytes, increasing the endothelial oxidative stress and transmigration of leukocytes into the smooth muscle region. This promotes generation of free radicals from the fibroblasts. In the current study, a diffusion‐ convection based transport model for arteriolar microcirculation has been developed to observe the concentration gradients of NO, superoxide and peroxynitrite during leukocyte adhesion and transmigration. The simulations show elevated levels of peroxynitrite within the leukocytes, along its vicinity and along the endothelium during the rolling process. Upon attachment their levels increase significantly even in the interstitial, luminal and smooth muscle region. Supported by NIH R01 HL084337.