Angiogenesis Flashcards
Describe endothelial cells.
- cuboidal cells which line all blood vessels
- have a surface area of 6000m2
- divide rarely in adult life
- capable of rapid division to specific stimuli
What is the main function of the cardiovascular system?
Role in transport of nutrients, metabolites, chemical mediators and waste products to and from cells. Role in gas exchange and important for immune system, homeostasis and body control.
What do vasculogenesis and angiogenesis do?
Form new blood vessels.
What are mural cells?
These are vascular smooth muscle cells and pericytes of the microcirculation.
What is the definition of vasculogenesis?
Vasculogenesis is defined as the differentiation of precursor cells called angioblasts into endothelial cells and the de novo formation of a primitive vascular network.
When does vasculogenesis occur?
Occurs during embryogenesis.
What is angiogenesis?
It is the formation of vascular sprouts from pre-existing vessels resulting in a highly branched vascular plexus.
The primary plexus is remodeled several times until a mature vascular system consisting of vessels of different diameters and functions are formed.
When does angiogenesis occur?
During development and postnatal life.
Give examples of angiogenesis occurring normally.
- during reproduction when blood vessels grow in the placenta.
- thickening of the endometrium in the uterus during menstruation.
- wound healing.
The healthy body controls angiogenesis through a series of “on” and “off” switches. What are the main on and off switches?
The main on switches = angiogenesis stimulating growth factors.
The main off switches = angiogenesis inhibitors.
Angiogenesis is turned off by the production of more inhibitors than stimulators.
How are pro-angiogenic processes switched off?
By upregulating anti-angiogenic factors.
Give some examples of pro-angiogenic factors.
VEGFs - vascular endothelial growth factors FGFs - fibroblast growth factors Angiopoietins PDGF - platelet derived growth factor TGF Beta - transforming growth factor B TNF Alpha CXC Chemokines EGF - epidermal growth factor CSF Insulin Erythropoietin Integrins MMPs
Give some examples of anti-angiogenic growth factors.
Endostatin Angiostatin Soluble FLT1 Tumstatin PEDF - pigment epithelium derived factor Platelet factor 4 Alphastatin Canstatin
What is the consequence of an injury?
Causes pro-angiogenic signaling mediators to be activated and their expression gets upregulated.
List some pathologies caused by upregulated angiogenesis.
Diabetic retinopathy Rheumatoid arthritis Atherosclerotic plaques Endometriosis Crohn's disease Psoriasis Uterine fibrosis Benign prostatic hypertrophy Cancer
Name two degenerative retianal diseases
AMD - age-related macular degeneration
Diabetic retinopathy
What is neovascularisation?
Formation of new blood vessels.
What is the difference between dry and wet AMD?
Dry AMD = the slow deterioration of the cells of the macula over many years as the retinal cells die off and are not renewed.
Wet AMD = presence of blood vessels which invade the retina, this neovascularisation causes irregular and immature blood vessels which leak, leading to the occlusion of the retina - leads to blindness.
The walls of coronary arteries are usually free from micro-vessels. But micro-vessels are present in atherosclerotic plaques. Describe the micro-vessels in the plaques.
Atherosclerotic plaques have dense networks of capillaries called vasa vasorum. These micro-vessels can cause hemorrhages - lead to blood clotting - decreased blood flow to heart muscle - results in heart attack.
How does angiogenesis contribute to plaque formation?
When blood vessels become thickened, hypoxia occurs in the area. This is a stimulus which switches on angiogenic processes. The thickened blood vessels start to make fragile micro vessels in order to supply oxygen to the area. these micro vessels are not matured and hence leak leading to clot formation.
What pro-angiogenic factors do endometriosis patients have?
- Elevated levels of vascular endothelial growth factor A (VEGF-A)
- Soluble vascular endothelial growth factor receptors 1 and 2 (VEGF-1 and VEGF-2)
- Angiopoietin 2 (Ang2)
- IL-4 = may induce angiogenesis
What happens during endometriosis?
Usually during normal menstruation the lining of the womb thickens but in endometriosis the lining starts to thicken outside of the womb. This is a painful condition. In bad endometriosis, lesions can cause tubal and ovarian adhesions.
What is Crohn’s disease?
This is a chronic inflammatory condition that affects both small and large intestines, resulting in extensive inflammation and ulceration of the colon. Soluble angiogenic factors are shown to be increased in Crohn’s disease patients.
Describe briefly, tumour angiogenesis.
Cancer is an angiogenic-dependent process. A growing tumpur needs an extensive vascular network to provide nutrients and oxygen. The new intratumoural blood vessels allows tumour cells to enter the circulation and to metastasize surrounding organs.