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Endothelial cell lineage determination and genetic basis of angiogenesis
The
formation and organization of blood vessels are essential to normal development
and tissue function. Activation or inhibition of angiogenesis may prove
therapeutic in diverse disease states, such as ischemic heart disease,
malignancy, and inflammatory disorders. We hope therefore to further elucidate
the molecular mechanisms underlying blood vessel biology.
Blood vessels
develop through vasculogenesis and angiogenesis. Vasculogenesis, the in
situ differentiation of precursor cells into endothelial cells, occurs
in early embryogenesis, as blood islands composed of progenitor cells
of hematopoeitic and endothelial cells arise from mesoderm. These endothelial
cell precursors differentiate and form the primordial vascular network.
In adults, increasing evidence points towards a continued potential for
vasculogenesis, conferred by a subpopulation of cells with the ability
to both self-renew and differentiate in response to biological stimuli.
Indeed, circulating endothelial precursor cells have been isolated and
may play roles in neovascularization and vascular injury response. Through
biochemical and molecular studies, we are investigating the function of
several cell surface markers present on these endothelial precursor cells.
The characterization of markers present on this cell population may facilitate
both the isolation of these cells for therapeutic studies and the understanding
of stem cell biology.
Angiogenesis, the sprouting and remodeling of vessels to create branched
vascular plexi, involves complex interactions between endothelial cells
and the supporting network of extracellular matrix, smooth muscle cells,
and growth factors. Using high-output transcriptional profiling, we have
identified several novel endothelial specific factors that may be involved
in cell adhesion, signal transduction, cytoskeletal alterations, and apoptosis.
The expression pattern of these factors during embryonic development will
be examined in order to place them in framework with other vascular developmental
markers. Furthermore, in vitro biochemical and tissue culture experiments
and in vivo knockout mice technology will be employed to investigate the
contribution of these factors to angiogenesis. Through these studies,
we hope to provide important insights into fundamental aspects of endothelial
cell biology and vascular development.
Other Research Areas:
-
Overview
- Athero
disease
- Endothelial
cells
- Smooth
muscle
cells
- Cell
remodeling
- Apelin
- Gene
Hunting
- SAPPHIRe
- Heart
developing
People involved in this project: