ANGIOGENESIS IN

HEALTH AND DISEASE

MODERATOR: Dr. Shilpa L.
 CONTENTS
• Introduction and history
• Types and mechanism
• Regulation of angiogenesis
• Modulators of angiogenesis
• Angiogenesis inducers
• Angiogenesis inhibitors
• Angiogenesis in health
• Angiogenesis in disease
• Tumour angiogenesis
• Therapeutic angiogenesis
• Conclusion
BLOOD VESSELS
 BLOOD VESSELS
•.
BLOOD VESSEL FORMATION
HISTORY
The Scottish anatomist and surgeon John Hunter provided
the first recorded scientific insights into the field of
angiogenesis. His observations suggested that proportionality
.
between vascularity and metabolic requirements occurs in
both health and disease.

The modern history of angiogenesis began with the work of

Judah Folkman, who hypothesized (and published in 1971)
that tumor growth is angiogenesis-dependent . Recognition
that control of angiogenesis could lead to cancer therapies
stimulated intensive research in the field.
VASCULOGENESIS
ANGIOGENESIS

The vascular network formation consists of multiple coordinated, sequential and interdependent steps mediated by a wide range of angiogenic factors, including growth factors, chemokines, angiogenic enzymes, endothelial specific receptors and adhesion
molecules.
.
ANGIOGENESIS- SPROUTING
REGULATION OF ANGIOGENESIS
• METABOLIC FACTORS:

• Capillary growth is proportional to metabolic

activity. Increase in metabolic activity stimulates
blood vessel growth

• Over oxygenation often leads to capillary

rarefaction in sedentary muscles by auto
regulatory vasoconstriction of arterioles.
.
• Long term increase in BP leads to vascular rarefaction by auto
regulatory vasoconstriction mechanism.

• Chronic exposure to hypoxia leads to increase in arterial

diameter,

• OXYGEN is the master signal in growth regulation of vascular

system.

• Role of Adenosine:
• Vasodialatory property- restores balance between O2 demand and
supply
MECHANOSENSORY COMPLEX
MODULATORS OF ANGIOGENESIS
ANGIOGENIC INDUCERS: GROWTH
FACTORS
The platelet-derived growth factor (PDGF)
Fibroblast growth factor
ANGIOGENIC INDUCERS: ADHESION
MOLECULES
PROTEASES
INHIBITORS OF ANGIOGENESIS
ANGIOGENESIS IN HEALTH
ANGIOGENESIS- A BALANCING ACT
• The healthy body controls angiogenesis through a series of on
and off switches:
• On switches– angiogenesis stimulating growth factors
• Off switches- angiogenesis inhibiting growth factors

• Most of the normal angiogenesis occurs during embryogenesis

and growth. Normally endothelial cells are quiescent and divides
only at the rate of one in every 10,000 endothelial cells.

• Angiogenesis occurs in the healthy body for healing wounds and

for restoring blood flow to tissues after injury or insult
.
•.
Exercise

• Angiogenesis is generally associated with aerobic exercise and 

endurance exercise.
• Angiogenesis causes changes that allow for greater nutrient
delivery over a long period of time.
• Capillaries are designed to provide maximum nutrient delivery
efficiency, so an increase in the number of capillaries allows the
network to deliver more nutrients in the same amount of time.
• And allows for greater oxygen exchange in the network.
ANGIOGENESIS IN DISEASE
• The common feature that is shared by both physiological as
well as pathological angiogenesis is that, formation of new
blood vessels is in response to demand for nutrients and
oxygen.

• But Pathological angiogenesis does not reach resolution after

the formation of blood vessel.

• Dysregulated angiogenesis is the characteristic feature of

pathological angiogenesis.
DISEASES CAUSED DUE TO EXCESSIVE
ANGIOGENESIS
DIABETIC RETINOPATHY
PSORIASIS
DISEASES CAUSED DUE TO
INSUFFICIENT ANGIOGENESIS
TUMOR ANGIOGENESIS
• Judah Folkman had proposed that tumor
growth and metastasis are dependent on
angiogenesis

• Tumor growth gets restricted in size owing

to the non-availability of nutrients and
oxygen

• Oxygen and nutrients cannot diffuse into

the core of the tumor thereby creating a
hypoxic situation. This in turn, lead to
events that initiates angiogenesis.
.
TUMOUR ANGIOGENESIS
• Three major steps
• Initiation of the angiogenic response
• Endothelial cell(EC) migration, proliferation and tube formation
• Finally the maturation of the neovasculature

• blocking of tumor angiogenesis could be developed as an

important therapeutic strategy to control tumor growth.

• In the absence of angiogenesis, tumor cells do not get nutrients

and oxygen and therefore become necrotic or apoptotic.
CELLULAR MECHANISM OF TUMOR ANGIOGENESIS
ANGIOGENESIS ASSAYS
• 1. In-vitro assays
-Proliferation assay
-Migration assay
-Tube formation assay
-Rat and mouse aortic ring assay
• 2. In-vivo assays
• -Corneal angiogenesis assay
• -Chick choreoallantoic membrane angiogenesis assay
• -Matrigel Plug assay
• The difficulties faced:
-ECs are heterogeneous
-In-vitro conditions rarely reflects in-vivo environment
THERAPEUTIC ANGIOGENESIS
• Antiangiogenic treatment can reduce a tumor mass back to
its avascular size
• It may not completely eliminate tumors that regress to
sizes no longer dependent on increased vascularity.
• The antiangiogenic agents may also be useful for prolonged
treatment to prevent regrowth of dormant
micrometastases.
• There are, however, sporadic reports of tumors that have
been completely eliminated by antiangiogenic therapy
alone.
THERAPEUTIC ANGIOGENESIS
Stimulation
Approved indication:
Chronic wound – diabetic ulcer
Experimental indication :
• Myocardial infarction
• Peripheral ischemia
• Cerebral ischemia
• Reconstructive surgery
• Gastoduodenal ulcer
Inhibition
Approved indication:
• Advanced cancer
• Ocular neovascularization
• Kaposi sarcoma
Experimental indication :
• Hemangioma
• Psoriasis
• Rheumatoid arthritis
• Endometriosis
• Atherosclerosis 
Bevacizumab
a humanised monoclonal antibody, precisely targets VEGF
.
.
CONCLUSIONS:
• The study of angiogenesis is making a profound impact on the
biological and medical world.
• The hope of being able to build new, functional, and durable blood
vessels in ischemic tissues, or conversely, to prevent their further
growth in malignant and inflamed tissues is becoming more realistic
every day.
• However, efforts to therapeutically stimulate new blood vessels have
significantly lagged behind those to inhibit angiogenesis.
• Better understanding of the underlying process will enable the
scientist to develop new drugs and therapies that will significantly
enhance our ability to treat intractable diseases, such as, cancer,
diabetes, and heart disease.
REFERENCES
• Robbins and Cotran Pathologic basis of disease-9th ed.
• Histology for pathologists,Stacey E Mills-3rd ed.
• Devita,Hellman,Rosenberg Cancer: Principles and Practice of
Oncology-8th ed.
• antatore FP, Maruotti N, Corrado A, Ribatti D. Angiogenesis
Dysregulation in the Pathogenesis of diseases. Biomed Res
Int.2017;5(1)26-32
• Chung, AS, Ferrara N. Developmental and Pathological
Angiogenesis. Annual Review of Cell and Developmental
Biology.2011;27(1)563–84.
• Internet picture sources
 THANK YOU 
Modulation of angiogenesis may have an impact on diseases in the twenty-first
century similar to that which the discovery of antibiotics had in the twentieth
century….