Cardiovascular Physiome

Introduction: Vascular Endothelial cells (ECs) play a major role to maintain blood flow. Important EC functions (e.g., such as macro-molecular transport, angiogenesis, vasomotor contorl and leukocyte transmigration) are strongly affected by mechanical stresses, such as fluid shear stress and cyclic stretch. Moreover, these EC functions are significantly related with nano- and micro-mechanics of EC. Methods: The Electric Cell-substrate Impedance Sensing (ECIS) system developed by Giaever and Keese (Nature, 1993) allows nano-scale measurements of cell-cell or cell-substrate distances. Atomic force microscope (AFM) is also a powerful tool for measurement the micro-mechanics of cells. We used these systems to evaluate the EC responses to the interaction between monocyte and EC or to shear stress. Results: Application of monocytic THP-1 cells to IL-1?-stimulated EC immediately decreased the EC-to-substrate electrical impedance, while the cell-to-cell resistance was unchanged (PNAS, 2002), indicating that EC adhesiveness to substrate was decreased following monocyte adhesion. The AFM measurement showed that increased EC deformability following monocyte adhesion. These results suggest that monocyte adhesion facilitates monocyte migration. When shear stress was applied to EC, the total electric impedance of EC peaked after 30 min at the onset of shear stress, but decreased below baseline after 1 hr. The impedance remained below baseline during next 10 hrs, but increased above baseline after 10 hrs. These changes may be closely related with changes in F-actin structure, redistribution of focal adhesion contacts, and mechanical properties of EC. We also established the experimental system to track migration of a single monocyte three-dimensionally (Atherosclerosis, 2005). Individual monocyte behavior was diverse and seemed to be closely related with mechanics of both monocytes and EC. Conclusions: Cell mechanics is one of the important determinant of cells functions and, nano- and micro-scale measurement technologies provide us important pathological and physiological information.