THE INFLUENCE OF MEMBRANE CHOLESTEROL-RELATED SHEAR STRESS MECHANOSENSITIVITY ON NEUTROPHIL FLOW BEHAVIOR

摘要: OF DISSERTATION THE INFLUENCE MEMBRANE CHOLESTEROL-RELATED SHEAR STRESS MECHANOSENSITIVITY ON NEUTROPHIL FLOW BEHAVIOR Hypercholesterolemia is a dominant risk factor for variety of cardiovascular diseases and involves chronic inflammatory component in which neutrophil activity plays critical role. Recently, fluid shear stress mechanotransduction has been established as control mechanism that regulates the neutrophils by reducing formation pseudopods surface expression CD18 integrins, thereby rendering these cells rounded, deformable, non-adhesive. This maintaining healthy circulation, because chronically activated not only release excess cytotoxic degradative agents but also exhibit reduced efficiency to pass through small vessels microcirculation leading increased microvascular resistance. We hypothesized aberrant mechanosensitivity due altered blood environment (i.e., plasma cholesterol) contributing elevated hemodynamic resistance associated with hypercholesterolemia. For this purpose, present work firstly showed sensitivity depends on cholesterol-dependent fluidity cell membrane, that, face hypercholesterolemia, highly correlated levels free cholesterol. The second part project demonstrated when subjected fields, leukocyte suspensions exhibited transient (within 10 min flow onset) time-dependent reductions their apparent viscosity. Moreover, shear-induced changes viscosity were influenced disturbances membrane cholesterol fashion similar pseudopod retraction. Finally, third provided evidence played role hypercholesterolemia-related impairment recovery response ischemia. In conclusion, results current first an important mechanotransducing capacity impaired may disturb rheology, elevations well cholesterol-linked perturbation be pathologic