ANGIOGENESIS
Angiogenesis
is the growth
of new blood vessels from pre-
existing vessels.
- occurs in the healthy body for healing
wounds and for
restoring blood flow to tissues after
injury; in females, to
rebuild the uterus lining, and during
pregnancy to build the
placenta
- also a fundamental step in the transition
of tumors from a
dormant state to a malignant one
Facts
& Figures
* The total surface area covered by these
cells in an adult is
1000-- roughly the size of a tennis court.
* If all the blood vessels in the body were
lined up end-to-
end, they would form a line that could
circle the earth twice.
* Blood vessel cells do not normally grow in
the healthy adult
they are normally inactive, or quiescent.
Two Types of Angiogenesis:
1. Sprouting
angiogenesis - vessel formation & growth as
entirely new vessels; involves
mural/pericytes & smooth
muscle cells
2. Intussusceptive/
splitting angiogenesis - the capillary wall
extends into the lumen to split a single vessel in two.
Vasculogenesis (spontaneous blood vessel formation) is
the process of blood vessel formation occurring by a de
novo production of endothelial cells; when endothelial
precursor cells (angioblasts –endothelial cells)
& smooth muscles (from myofibroblasts) migrate
and
differentiate in response to local cues (such
as growth
factors and extracellular matrix) to form
new blood vessels.
Arteriogenesis is the formation of medium-sized blood
vessels possessing tunica media &
adventitia.
- also involves increase in the diameter of existing
arterial vessels.
- common response to physical exercise
&
atherosclerosis
Origin: intermediate mesoderm, lateral plate mesoderm
Terms:
*
endothelial cells –line the interior surface
of blood
vessels & lymphatic vessels,
* pericytes/Rouget’s/mural
cells –contractile cells that wrap
around the endothelial cells of capillaries and venules
*
angioblasts – endothelial progenitor cells; one of the two
products formed from hemangioblasts (the other being
Control:
The healthy body controls
angiogenesis through a series of "on" and "off" switches:
- The main "on"
switches are known as angiogenesis-stimulating growth factors
- The main "off
switches" are known as angiogenesis inhibitors
The normal, healthy body
maintains a perfect balance of angiogenesis modulators. In general,
angiogenesis is "turned off" by the production of more inhibitors
than stimulators.
Chemical Signals:
Angiogenic Growth Factors
*
Fibroblast Growth Factor (FGF) – initiate a process of
mitogenic activity critical for the
growth of endothelial cells,
fibroblasts, and smooth muscle cells.
- promotes healing in chronic wounds of
DM patients
* vascular
endothelial growth factors (VEGFs) – increase the
number of capillaries in a given network
* at least 20 other GFs
Angiogenic Inhibitors:
* Angioarrestin – to inhibit proliferation
induced by VEGF of
vascular endothelial cells derived from
different vessel type
* Angiostatin (plasminogen
fragment) – involve inhibition of
endothelial cell migration, proliferation and induction of
* at
least 30 (300 to date) other angiogenic inhibitors
Excessive angiogenesis:
* in cancer, diabetic blindness, age-related macular
degeneration, rheumatoid arthritis,
psoriasis, and more
than 70 other conditions.
- diseased
cells produce abnormal amounts of angiogenic
GFs, overwhelming the effects of
angiogenesis inhibitors.
- Anti-angiogenic therapies –
starve diseased cells
Insufficient angiogenesis:
* in coronary artery disease, stroke,
ischemic heart
disease, and chronic wounds
- cannot produce adequate amounts of
angiogenic GFs
·
Therapeutic
angiogenesis to stimulate angiogenesis,
improve
perfusion, deliver survival factors to sites of
tissue repair, mobilize regenerative stem cell
populations, and ultimately, restore form and
function
- possibly
for regeneration of nerves
