| Research Abstract |
(1) In the present study, we have established an in vitro model of "blood brain barrier". With vascular endothelial cell, pericyte and astroglial cell co-culture systems, the barrier as well as transport activities selective to brain vessels were reconstituted, which passed polycationic albumin but excluded native albumin or inulin in the physiological polarity. This model would seem to be useful in screeeing substances that could act on the central nervous system and in evaluating their delivery into the brain. The present study has also demonstrated that astroglial cells are capable of "transdifferentiating "non-brain-type endothelial cells into brain-type ones : human umbilical vein endothelial cells co-cultured with astroglial cells did express the brain endothelium-specific genes, including those for gamma-transglutamyl transpeptidase, transferrin receptor and P-glycoprotein, and aquired the anti-inulin barrier propert. Although we failed to develop brain-specific transport vectors, new discoveries (2) that advanced glycation endproducts selectively injure pericytes through interactions with their cell-surface receptors, (3) that endothelial cells and vascular smooth muscle cells possess the devices both for synthesizing and for responding to aldosterone, a steroid implicated in the regulation of blood pressure, and (4) that hypoxia-induced proliferation of vascular cells in mediated by autocrine vascular endothelial growth factor, were made during the course of this study, and we have thus proposed novel mechanisms underlying the development and progression of various human vascular disorders including diabetic microangiopathy, hypertension and angiogenesis.
|
