What is angiogenesis, its types, physiological & pathological angiogenesis, antiangiogenic agents to treat cancer.

1. ANGIOGENESIS
Presented By
Name : Dibyendu Dutta
M. Pharm, Pharmacology, 1st Year, 1st Semester
NSHM KNOWLEDGE CAMPUS, KOLKATA
GROUP OF INSTITUTIONS

2. INTRODUCTION
 The word “Angio” means blood vessels while “genesis” means creation, i.e.
Angiogenesis is the formation of new blood vessels from pre-existing vessels.
 Angiogenesis is a normal process in growth and development, as well as in
wound healing.
 Angiogenesis mainly occurs by two ways:
1. Sprouting angiogensis
2. Intussusceptive angiogenesis

3. SPROUTING ANGIOGENESIS
It occurs in several well-characterized stages:
1. Activation of VEGF receptors of endothelial cells present in pre-existing
veins.
2. The activated endothelial cells escape from the original vessel walls by help
of protease.
3. Proliferation of endothelial cells into the surrounding matrix.
4. Migration of endothelial towards the source of the angiogenic stimulus
5. Re-organisation of endothelial cells to form tubules with a central lumen &
interconnection of new tubules to form a branched network.

4. INTUSSUSCEPTIVE ANGIOGENESIS
Intussusceptive, also known as Splitting angiogenesis i.e. a single vessel split in two.
There are four phases of intussusceptive angiogenesis.
1. Two opposing capillary walls establish a zone of contact.
2. Perforation of vessel bilayer to allow growth factors and cells to penetrate into the
lumen.
3. Formation of a core at the zone of contact between two vessels & is filled with
pericytes and myofibroblasts.
4. The core is fleshed out with no alterations to the basic structure.

6. STIMULATORS OF ANGIOGENESIS
 Basic fibroblast growth factor (bFGF)
 Vascular endothelial growth factor (VEGF)
 Angiogenin
 Epidermal growth factor
 Interleukin 8
 Granulocyte colony stimulating factor
 Placental growth factor
 Platelet-derived endothelial growth factor
 Tumor necrosis factor alpha (TNF-α)

7. INHIBITORS OFANGIOGENESIS
Naturally occurring angiogenic
inhibitors
Thrombospondin, Interferon,
Metalloproteinase inhbitors
Tumor derived inhibitors Angiostatin, Endostatin
Pharmacological inhibitors Thalidomide,
Carboxyamidotriazole (CAI)
Synthetic inhibitors Synthetic Protease Inhibitors,
Anti-adhesive Peptides [3]

8. PHYSIOLOGICAL ANGIOGENESIS
Some of the normal situations where angiogenesis is important include:
• Wound healing.
• Formation of Placenta during Pregnancy.
• Regeneration of endometrium after menstruation.
• Heart attack: New coronary vessels could repair damaged heart.
• Neurodegenarative ills: An increased blood supply could minimize neuronal
damage in brain.
• Angiogenesis can bypass the blood clots in legs and improve circulation.
Angiogenesis in
uterine lining
Angiogenesis in tissue
during wound healing

9. PATHOLOGICAL ANGIOGENESIS
The imbalance between the angiogenic factors & the anti-angiogenic agents can
cause several complications, such as:

10. THE SWITCH OFF & SWITCH ON
EFFECT
 When tumor tissues require fuel (nutrients and oxygen), angiogenesis is
stimulated.
 The switch to the angiogenic phenotype involves a change in the local
equilibrium between positive and negative regulators of angiogenesis.

11. CANCER TREATMENT WITH ANTI-
ANGIOGENIC AGENTS
 For the metastatic spread of cancer tissue,
growth of vascular network is important.
 Angiogenesis plays the vital role in this step
by providing nutrients & oxygen.
 Angiogenesis is regulated by both activator &
inhibitor molecules.
 The imbalance between positive & negative
regulator of angiogenesis produces a signal.
 The signaling initiates certain genes that make
proteins which promotes the growth of blood
vessels.

12. Continued…
 The scientists are studying on natural &
synthetic angiogenic inhibitors to
prevent or slow the growth of cancer.
 Cytotoxic chemotherapy suppresses the
cancer directly.
 The anti-angiogenic therapy suppress it
indirectly by depriving the cells of
nutrients & oxygen.
 Thus the combination of chemotherapy
along with anti-angiogenic therapy
might be beneficial for the treatment of
cancer.

13. Continued…
 For example, bevacizumab (Avastin®) is a monoclonal antibody, that
binds to VEGF receptors.
 Avastin is designed to directly bind to VEGF extracellularly to prevent
interaction with VEGF receptors (VEGFRs) on the surface of endothelial
cells, and thereby may inhibit VEGF's angiogenic activity