Angiogenesis
Md. Abdur Rakib, Ph.D Associate Professor
Department of Biochemistry and Molecular Biology University of Rajshahi
Structure of vessels and capillaries
Monocellular layer of endothelial cells Small artery:
Capillary: endothelial cell, basal lamina, pericytes
Angiogenesis:
Sprouting of cells from mature endothelial cells of the vessel wall
Mouse cornea:
wounding induces angiogenesis,
chemotactic response to
angiogenic factors
(Secretion of proteases, resolution of Basal lamina, migration towards Chemotactic gradient, proliferation, Tube formation)
VEGF is factor largely specific for endothelial cells,
bFGF can also induce, not specific for EC)
Sprouting towards chemotactic gradient: VEGF
Vasculogenesis- is the formation of blood vessel de novo from stem cells or by sprouting/intussusseption during embryogenesis.
Neo-vasculature Formation
Angiogenesis- is the formation of blood vessel via extension or remodeling from existing capillaries. wound healing, menstrual cycle, tumor-angiogenesis…
Blood vessel formation
Angiogenesis is a normal and necessary process
Angiogenesis is pivotal in:
Tissue growth and development.
Plays role in normal physiology
Wound healing,
Female reproductive cycle
Inflammation and embryogenesis.
Angiogenesis and Cancer
Tumor angiogenesis is not programmed like embryogenesis Instead it is dependent upon local signals.
Tumor blood vessels are often torturous and leaky.
Many abnormalities.
Angiogenesis controls tumor growth
• Tumor can stay in a ‘dormant’ state for long periods.
• The angiogenic switch allows for growth of the tumor to occur.
• Increased angiogenesis correlates with worse prognosis.
The Angiogenesis Signaling Cascade
The Angiogenesis Signaling Cascade
VEGF – Vascular endothelial growth factors VEGF-A – Crucial mediator of angiogenesis
VEGF-R – Receptors for vascular endothelial growth factors Angiopoietins (Ang-1, 2)
Tie- 2 – receptor for Ang-1, -2 FGFs – fibroblast growth factors
PDGF – platelet-derived growth factor
Major growth factors and receptors involved in blood
vessels formation.
VEGF- A key to angiogenesis
VEGF (Vascular endothelial growth factor), One of the most important angiogenic factor, discovered by Dr. Napoleone Ferrara and by Dr. Jean Plouet in 1989
• At least 5 different forms of VEGF. Binds to its receptors VEGFR 1, 2 or 3.
• The receptors are tyrosine kinases.
• VEGF also causes vascular permeability, which leads to vessel leakiness.
VEGF helps in the formation of new blood vessels that support
tumor growth.
VEGF is not the whole story
There are several other growth factors that increase angiogenesis (1-e.
bFGF).
Not all parts of a vascularized tumor actually gets vessels, Instead sometimes necrosis occurs.
Inhibitors of Angiogenesis
• Angiostatin
• Endostatin
• Interferon
• Tissue inhibitors of metalloproteinases (TIMP 1,2,3)
