Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1238 Chapter 22: Stem Cells and Tissue Renewal
HIGH O 2
LOW O 2
HIGH HIF1α
Figure 22–26 The regulatory mechanism
controlling blood vessel growth
according to a tissue’s need for oxygen.
Lack of oxygen triggers the secretion of
VEGF, which stimulates angiogenesis.
LOW HIF1α
tissue cells
capillary
sprout
secreted
VEGF
small blood vessel
Signals from Endothelial Cells Control Recruitment of Pericytes
and Smooth Muscle Cells to Form the Vessel Wall
The vascular network is continually remodeled as it grows and adapts. A newly
formed vessel may enlarge; or it may sprout side branches; or it may regress.
Smooth muscle and other connective-tissue cells that pack themselves around
the endothelium (see Figure 22–23) help to stabilize vessels as they enlarge. This
process of vessel wall formation begins with recruitment of pericytes. Small numbers
of these cells travel outward in company with the stalk cells of each endothelial
sprout. The recruitment and proliferation of pericytes and smooth muscle
MBoC6 m23.35/22.26
cells to form a vessel wall depend on platelet-derived growth factor-B (PDGF-B)
secreted by the endothelial cells and on PDGF receptors in the pericytes and
smooth muscle cells. In mutants lacking this signal protein or its receptor, these
vessel wall cells are missing in many regions. As a result, the embryonic blood
vessels develop microaneurysms—microscopic pathological dilatations—that
eventually rupture, as well as other abnormalities, reflecting the importance of
signals exchanged in both directions between the exterior cells of the wall and the
endothelial cells.
Summary
Endothelial cells are the fundamental elements of the vascular system. They form a
single cell layer that lines all blood vessels and lymphatics and regulates exchanges
between the bloodstream and the surrounding tissues. New vessels originate as
endothelial sprouts from the walls of existing small vessels. A specialized motile
endothelial tip cell at the leading edge of each sprout puts out filopodia that respond
to gradients of guidance molecules in the environment, leading the growth of the
sprout in much the same way as the growth cone of a neuron is led. The endothelial
stalk cells following behind become hollowed out to form a capillary tube. Signals
from endothelial cells organize the growth and development of the connectivetissue
cells that form the surrounding layers of the vessel wall.
A homeostatic mechanism ensures that blood vessels permeate every region of
the body. Cells that are short of oxygen increase their concentration of hypoxiainducible
factor 1α (HIF1α), which stimulates the production of vascular endothelial
growth factor (VEGF). VEGF acts on endothelial cells, causing them to proliferate
and invade the hypoxic tissue to supply it with new blood vessels. As new vessels
enlarge, they recruit increasing numbers of pericytes—cells that cling to the outside
of the endothelial tube and mature into the smooth muscle coat that is needed to
give the vessel strength.