ENDOTHELIAL-CELLS IN CULTURE - AN EXPERIMENTAL-MODEL FOR THE STUDY OFVASCULAR DYSFUNCTIONS

Culture of endothelial cells started two decades ago and is now a usef ul tool in understanding endothelial physiology and the study of the i nteraction of endothelial cells with blood cells and various mediators . In vitro proliferation can be measured by [H-3]thymidine incorporati on in defined conditions and gives reproducible results. Endothelial c ells can be activated by several stimuli, including cytokines such as tumor necrosis factor-alpha and interleukin-1. Part of endothelial cel l activation is defined by expression or overexpression of leukocyte a dhesion molecules. Intracellular adhesion molecule (ICAM), E-selectin and vascular adhesion molecule (VCAM) are receptor molecules for leuko cyte adhesion. Leukocyte adhesion to endothelium can be measured in st atic but also in theologically defined flow conditions. Normal red blo od cells (RBCs) do not adhere to endothelium, while RBC from patients with sickle cell anemia, diabetes mellitus, and malaria have an increa sed adhesion to endothelium which is mediated by specific VCAM, recept or for advanced glycated end-products (RAGE), and ICAM, respectively. Binding of blood cells or activation by cytokine is followed by a seri es of reactions in endothelial cells associated with the modulation of prostacyclin, nitric oxide, tissue factor, and cytokine production. M odification of endothelial cell functions in culture is correlated to in vivo alteration of vascular wall properties, further supporting the se cells in culture as a relevant experimental model.