Atherosclerosis is an asymptomatic condition with potentially fatal consequences. However, the pathophysiological mechanisms behind the development of disease are not well understood. The accumulated evidence from clinical and experimental studies suggests that an inflammatory response is the key factor in initiation and development of atherosclerosis. A new novel peptide, called Pepitem (Peptide Inhibitor of Trans-Endothelial Migration), has been discovered in our lab which down regulates T cell recruitment during inflammation. The mechanism by which pepitem acts is still unknown but work in our lab suggests that it is released in response adiponectin binding to the adiponectin receptors (AR1 & AR2) present on B cells. It then stimulates the endothelium through a specific receptor which subsequently inhibits transmigration of T lymphocytes. We hypothesized that pepitem mediated T cell recruitment is impaired in atherosclerosis patients and treating their lymphocytes with pepitem would restore this mechanism. The static adhesion assay showed no effect of pepitem on lymphocyte transmigration (P<0.01). However, flow-cytometric studies suggested higher expression of adiponectin receptors in patients than controls (P=0.2). These data suggests that in atherosclerosis patients, the immuno-regulatory pathway which controls the magnitude of an inflammatory response is faulty, leading to inappropriate levels of inflammation.
- CARDIAC PROCEDURES AND THERAPY
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