ABSTRACT
The human body is organised hierarchically into organ systems which perform major physiological functions such as circulation, respiration, and digestion. Among these, the circulatory system delivers a continual flow of blood to each functional unit while
4.1 Introduction .................................................................................................... 51 4.2 Materials and Methods ................................................................................... 52
4.2.1 Cell Culture ........................................................................................ 52 4.2.2 Flow Chamber Studies on EC Function ............................................. 53
4.3 Effects of Physical and Chemical Factors on ECs ..........................................54 4.3.1 Effect of Shear Stress on EC Morphology .........................................54 4.3.2 Effect of Shear Stress Magnitude on Macromolecule Uptake
into ECs .............................................................................................. 55 4.3.3 Effect of Shear Stress on Albumin Permeability
across an EC Monolayer ..................................................................... 55 4.3.4 Effect of Shear Stress on Mitochondrial Membrane Potential ........... 58 4.3.5 Effect of Shear Stress on EC Networks .............................................. 58 4.3.6 Effect of Shear Stress on Intracellular Calcium in ECs .....................60 4.3.7 Effect of Disturbed Flow on EC Morphology
and Macromolecule Uptake ................................................................ 63 4.3.8 Effect of Concentration Gradients for Growth Factors on EC
Network Morphology..........................................................................66 4.4 Conclusions .....................................................................................................66 References ................................................................................................................ 67
facilitating the filtration of metabolites and waste products. The circulatory system also serves as a conduit for communication between distant tissues through the transport of hormones. Oxygen and hormone concentrations in the blood, blood pressure, and blood flow are known to change when the external environment changes. The functions and morphology of the vascular system are regulated by haemodynamic stresses such as fluid frictional force (shear stress) induced by blood flow (Skalak and Price 1996). Wall shear stress affects vascular remodelling; Kamiya and Togawa (1980) report that wall shear stress due to blood flow induces adaptive changes in the blood vessel lumen in vivo, such that a constant wall shear stress is maintained within physiological bounds. Wall shear stress is thus a major factor influencing adaptive vessel regulation for physiological processes. To understand variations in human adaptability, the detailed mechanisms of human adaptability must be elucidated. Understanding adaptability of this system is constrained by the limited possibility of direct measurement. More generally, understanding what responses and adaptations to the external environment occur inside the body is not easily determined, as many factors interact with each other in complex ways. Simplification of systems is useful for understanding physiological mechanisms in detail. To this end, cell (tissue) studies are useful, since they can control experimental variables. With respect to the blood vessels of the circulatory system, endothelial cells (ECs) line the inner surface of blood vessels and are continuously exposed to physical factors such as fluid frictional force (shear stress) induced by blood flow and are also exposed to chemical factors such as oxygen and hormones in the blood.
