Altering Angiogenesis
ngiogenesis is the formation of new
blood vessels. Under the influence of
specific growth factors, endothelial
cells divide and assemble into the tubules that
form capillaries as well as the innermost linings
of larger blood vessels. In normal development,
angiogenesis is crucial to build a blood sup-
ply to serve a growing body. New blood vessels
deliver nutrients, hormones, and growth fac-
tors to tissues and remove wastes. Angiogenesis
is also essential for healing. After a heart attack,
for example, new vessels form in the remaining
healthy cardiac muscle to supply blood.
As with most biological processes, angio-
genesis must be highly controlled. Excess, defi-
cient, or inappropriate angiogenesis can cause,
or worsen, a variety of illnesses. By understand-
ing how angiogenesis proceeds, researchers are
developing ways to direct new blood vessel for-
mation, with two speciF
c applications—healing
hearts and starving cancerous tumors.
Heart Attacks:
Promoting Angiogenesis
An errant clot blocks a coronary artery. Within
seconds, the localized lack of oxygen stimulates
muscle cells to release hypoxia-inducible factor
(HI±-1). This protein activates several genes whose
products restore homeostasis by stimulating gly-
colysis (anaerobic respiration); signalling the kid-
neys to produce erythropoietin, which boosts the
red blood cell supply; and triggering angiogenesis
by turning on production of vascular endothelial
growth factor (VEG±). The growth factor stimulates
certain cells to proliferate and aggregate to form
capillaries, which, eventually, restore some blood
flow to the blocked cardiac muscle. ±ibroblast
growth factor also assists in angiogenesis.
When natural angiogenesis isn’t sufficient,
part of the heart dies. Coronary bypass surgery
and angioplasty are treatments that restore blood
ow, but for patients who cannot undergo these
procedures or whose blockages are in vessels
too narrow or difficult to reach, harnessing and
targeting angiogenesis may help to save starved
heart parts. One approach is to package growth
factors in time-release capsules implanted near
small vessels while large ones are being surgi-
cally bypassed. In one clinical trial, this technique
increased blood ²
ow to the area and halted chest
pain. Another strategy is gene therapy, which
delivers the genes that encode the growth fac-
tors to oxygen-starved areas of the heart.
Cancer Treatment:
Preventing Angiogenesis
A tumor surrounds itself with blood vessels.
Once it reaches the size of a pinhead, a tumor
secretes growth factors that stimulate nearby
capillaries to sprout new branches that extend
toward it. Endothelial cells that are part of the
tumor assemble into sheets, roll into tubules,
and, eventually, snake out of the tumor as new
capillaries. Other cancer cells wrap around the
capillaries, spreading out on this sca³
olding into
nearby tissues. Some cancer cells enter blood
vessels and travel to other parts of the body.
±or a time, maybe even years, these secondary
tumors stay small, adhering to the outsides of
the blood vessels that delivered them. But when
the primary tumor is removed, angiogenesis-
promoting growth factors wash over the tumors,
and they grow.
In the 1970s, researchers began to study
the antiangiogenesis factors that keep second-
ary tumors small, to develop them as cancer
treatments. The first antiangiogenesis drug to
treat cancer became available in 2004, for col-
orectal cancer that has spread to other organs.
It extends life an average of five months, when
combined with standard chemotherapy, com-
pared to chemotherapy alone. The drug, a
monoclonal antibody against VEG±, may be
useful in treating breast cancer too. Today sev-
eral antiangiogenesis drugs are used to treat
Arteries and Arterioles
¯z) are strong, elastic vessels adapted for
carrying the blood away from the heart under high pres-
sure. These vessels subdivide into progressively thinner
tubes and eventually give rise to the ±
ner branched
The wall of an artery consists of three distinct layers, or
shown in
f gure 15.25
. The innermost tunic, tunica
interna (intima), is composed of a layer of simple squamous
epithelium, called
that rests on a connective
tissue membrane rich in elastic and collagenous ±
The endothelial lining of an artery provides a smooth
surface that allows blood cells and platelets to fl ow through
without being damaged. Additionally, endothelium helps
prevent blood clotting by secreting biochemicals that inhibit
platelet aggregation (see chapter 14, p. 542). Endothelium
also may help regulate local blood fl ow by secreting sub-
stances that either dilate or constrict blood vessels. For
include arteries, arterioles, capillaries, venules, and veins.
The arteries and arterioles conduct blood away from the
ventricles of the heart and lead to the capillaries, where sub-
stances are exchanged between blood and the body cells.
Venules and veins return blood from the capillaries to the
atria. From Science to Technology 15.2 describes angiogen-
esis, the formation of new blood vessels in the body.
An intriguing new way to study angiogenesis is to grow human
capillaries in mice. Human endothelial cells cultured in a labora-
tory dish aggregate into tiny spheres. Researchers embedded the
spheres in a gel and subcutaneously injected the material into mice
that lack immune systems, along with growth factors. Human capil-
laries formed under the mouse skin and joined the blood vessels of
the mice. The method is being used to study angiogenesis as well as
engineering replacement vascular tissue.
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