ENDOTHELIAL PERMSELECTIVITY DURING NORMAL ANGIOGENESIS

Project Details

Description

This proposal aims to examine, for the first time, the correlation
between endothelial ultrastructural differentiation and macromolecular
permselectivity during normal angiogenesis. In particular, the role of
biomolecular differentiation of the endothelial glycocalyx in modulating
the access of macromolecules to the junctional clefts and plasmalemmal
vesicles, during their concomitant ultrastructural differentiation, will
be evaluated. The extraembryonic microcirculation of the chick
chorioallantoic membrane (CAM), which requires neither anesthesia nor
surgical manipulation for direct microscopic observation, will serve as
models of angiogenesis. Evaluations of precapillary, capillary, and
postcapillary segments at days 6, 10, 14, and 18 of embryogenesis will
be approached, in part, by intravital fluorescence microscopy and the
integrated optical intensity technique to assess differential rates of
extravasation of a series of graded molecular weight FITC-dextrans. The
measured rates will provide an index of differentiation of endothelial
permselectivity during normal angiogenesis. Ultrastructural morphometric
detection of these same dextrans by colloidal gold immunocytochemistry
will serve to correlate differentiation of endothelial plasmalemmal
vesicles and junctional clefts with macromolecular permselectivity.
Ultrastructural profiles of specific lectins and charged markers within
the endothelial glycocalyx during the stages of endothelial
cytodifferentiation will complete the analysis of the paracellular and
vesicular pathways. Thus, the influence of biomolecular differentiation
of the glucocalyx on the regulation of macromolecular access to these
pathways will be evaluated. In addition, the effects of histamine on the
glycoconjugate microdomains within the glycocalyx, and hence, on
macromolecular transport will be tested. Taken as a whole, these data
on normal angiogenesis will serve to provide the basis for understanding
the derangements that occur during pathologic angiogenesis associated
with wound healing and tumorigenesis.
StatusFinished
Effective start/end date2/1/923/31/01

Funding

  • National Institutes of Health
  • National Institutes of Health: $194,280.00
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health: $203,559.00
  • National Institutes of Health: $210,206.00

ASJC

  • Medicine(all)

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