Lecture 7: Blood Disorders Flashcards
What are the processes involved in the formation of capillaries and lymphatics?
- Vasculogenesis: formation of blood vessels from precursor cells (angioblasts) or endothelial progenitor cells
- Angiogenesis: sprouting and branching of new blood vessels from pre-existing ones, typically in response to physiological or pathological stimuli.
- Lymphangiogenesis: formation of new lymphatic vessels from lymphatic endothelial progenitor cells, similar to angiogenesis but specific to lymphatic vessels.
What is arterogenesis, and how does it relate to the formation of arteries?
- Small arterioles or collateral arteries remodel and enlarge to form mature arteries, often in response to changes in blood flow or ischemic conditions.
- Involves the structural adaptation of existing vessels rather than de novo formation.
What processes are involved in vein formation?
- Vasculogenesis and angiogenesis, similar to the formation of capillaries and arteries.
- However, the specific mechanisms and regulatory factors governing vein development may differ from those of arteries.
What is angiogenesis, and when does it occur?
- The process of forming new blood vessels from pre-existing ones, typically occurring in response to various physiological or pathological stimuli.
- Can occcur as a result of trauma, embolism (blockage of arteries), neoplasia (tumor growth), diabetes, or during the regeneration of tissues such as the endometrium after menstruation or in instances of normal growth.
How do cancers form their own blood vessels through angiogenesis?
- Cancers induce angiogenesis to create new blood vessels that supply nutrients and oxygen to support tumor growth.
- Tumor cells release signaling molecules called angiogenic factors, such as vascular endothelial growth factor (VEGF),
- These signaling molecules stimulate nearby blood vessels to sprout and grow toward the tumor.
- This process allows tumors to establish a network of blood vessels, enabling their sustained growth and metastasis
What is the role of endothelial cells in blood vessel formation?
Grow in an ordered manner and participate in processes like sprouting or intussusceptive growth to generate new vessels.
What marker do endothelial cells contain, and what is its significance?
CD34 marker
What is sprouting in angiogenesis?
- A single capillary generates a sprout of solid endothelium that grows outward.
- This sprout eventually forms a lumen, resulting in the formation of two capillaries.
Describe the steps involved in sprouting angiogenesis.
- Endothelial cells respond to cues → extending filopodia, similar to fibroblast cells.
- Fibroblast cells search for suitable places and substrates to grow upon → formation of new blood vessels.
What is intussusceptive angiogenesis?
- A single capillary develops a growth down its center.
- This growth eventually forms a lumen → splitting of the capillary into two.
What is the stimulus for angiogenesis?
- Ischemia (lack of blood supply to tissues)
- Often occurs in growing tissues that outstrip their blood supply or in areas where blood flow is compromised.
How does ischemia lead to angiogenesis?
Ischemia in growing tissues → reduction of oxygen supply → hypoxia
How does hypoxia regulate gene expression?
- Hypoxia → stimulates the expression of genes that encode pro-angiogenic factors → formation of new blood vessels to restore oxygen delivery to the affected tissues
- When oxygen is plentiful, these genes are typically inactive.
What role does EPO play in response to hypoxia?
- Hypoxia stimulates the synthesis of erythropoietin (EPO) in the kidneys.
- EPO is released into the bloodstream and travels to the bone marrow, where it promotes RBC production
- EPO can stimulate the growth of endothelial cells → angiogenesis
What transcription factors are involved in regulating gene expression in response to hypoxia?
HIF-α and HIF-β
How does oxygen availability affect the stability of HIF complexes?
- High oxygen levels: part of the HIF-αβ complex is targeted for destruction.
- Hypoxia: HIF-α is stabilized → form a complex with HIF-β → regulate gene expression related to angiogenesis
What is the role of VEGF in angiogenesis?
- Vascular endothelial growth factor
- It acts as a growth factor that binds to its receptor, which is a receptor tyrosine kinase.
- This binding stimulates endothelial cells to proliferate and form new blood vessels.
Where is the receptor for VEGF typically found, and what does this imply about VEGF’s action?
- The receptor for VEGF is primarily found on endothelial cells.
- Indicates that VEGF selectively promotes the growth and function of endothelial cells, driving angiogenesis specifically in areas where new blood vessel formation is needed, such as in ischemic tissues.
