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Vascular remodeling, endothelial-smooth muscle cell communication
Vascular development
requires the sequential expression of genes leading to formation of functional
blood vessels. This process is important during embryonic development
(vasculogenesis) and for the formation or remodeling of blood vessels
in adults (angiogenesis). Vascular development is initiated by differentiation
of pluripotent stem cells into endothelial precursor cells (angioblast)
and subsequently into differentiated endothelial cells that form endothelial
tubes. Tube formation is followed by recruitment of pericytes and their
differentiation into vascular smooth muscle cells (VSMC). Growth factors
including PDGF, bFGF, VEGF, Angiopoietin-1, and TGF-b, adhesion molecules
and extracellular matrix (ECM) proteins mediate the proliferation and
migration of cells to the proper location. VSMC stabilize the endothelial
lining by inhibiting endothelial cell proliferation, and production of
ECM. They also contribute to hemostatic control and protect the new vessel
against rupture.
Transcription factors have been shown to be key regulators for vascular
development. The Quertermous lab is interested in identifying and elucidating
the role of transcription factors in vascular development. Targeted gene
disruption and overexpression studies have revealed the importance of
transcription factors for vascular development. For example, mice deficient
in the zinc finger transcription factor LKLF develops abnormalities in
the smooth muscle architecture of the tunica media with a lack of recruitment
of vascular smooth muscle cells leading to aneurysm, rupture of blood
vessel and early embryonic death. Another example is the targeted disruption
of the AP-1 transcription factor family member Fra1 that leads to abnormalities
in embryonic vascularization. The overexpression of the homeobox transcription
factor hhex in zebrafish leads to enhanced endothelial and erythroid differentiation.
Understanding the role of transcription factors for vascular development
will likely result in novel therapies for cardiovascular disease.
Other Research Areas:
-
Overview
- Athero
disease
- Endothelial
cells
- Smooth
muscle
cells
- Cell
remodeling
- Apelin
- Gene
Hunting
- SAPPHIRe
- Heart
developing
People involved in this project: