CVS 17: Vascular Endothelium Flashcards
What is atherosclerosis and which arteries does it particularly affect?
- Build up of fibrous and fatty material inside the arteries and is the underlying condition that causes CHD
- those which supply the head, brain and legs
What sort of disease is atherosclerosis?
A chronic inflammatory disease
What are the steps causing atherosclerosis?
- Endothelial dysfunction in atherosclerosis leads to increased permeability, leukocytes migration and adhesion under the endothelium
- Fatty-streak formation and foam cell formation
- Formation of an advanced and complicated lesion where a necrotic core and fibrous cap is formed with macrophage accumulation
- Angiogenesis to supply the new mass
What are the three layers of blood vessels? Which vessels are exceptions to the three layer structures
- Tunica intima- endothelium
- Tunica media- smooth muscle cells
- Tunica adventitia- vasa vasorum, nerves
**capillaries and venules
What is contact inhibition?
Formation of a monolayer by the endothelial cells
what is heterogeneity in terms of endothelial cells?
Not all endothelial cells are the same
Describe the structure of endothelial cells
Very flat
1-2μm which and 10-20μm in diameter
Name the four critical functions of endothelial cells
- inflammation
- vascular tone and permeability
- angiogenesis
- thrombosis and haemostasis
What state are healthy endothelial cells in?
- anti-inflammatory
- anti- thrombotic
- anti- proliferative
What state are endothelial cells in during inflammation?
- pro-inflammatory
- pro-thrombotic
- pro-angiogenic
What do leukocytes normally adhere to during inflammation?
- leukocytes adhere to the endothelium of post-capillary venules and transmigrate into tissues
What goes wrong with leukocyte recruitment during atherosclerosis?
- leukocytes adhere to the activated endothelium of large arteries
- they get stuck in the sub endothelial space
- newly formed post-capillary venues at the base of lesions = further entry
Summarise the process of transmigration, diapedesis and chemotaxis
- Rolling- weak selectin binding
- Activation- activate integrin binding
- Firm adhesion- integrin binding with ICAM-1 on endothelial cells
- Diapedesis- paracellular–> transcellular transmigration
What is the function of VE-cadherins for transmigration of leukocytes across the endothelium?
- VE-cadherin (vascular endothelial cadherins) acts as a zipper
- allow cell membranes to bind in a homophilic way
- leukocytes has to unzip the cadherins to get through
- allows substances to get through without monolayer falling apart
What happens if you have a mutation in VE-caderins?
Not compatible with life
Can’t fight off infections
What is the difference between the transmigration process between venues and arteries?
- Capillary- endothelial cells surrounded by basement membrane and pericytes (TM is possible) just uses enzymes to get through BM
- Post-capillary venues- similar to capillary but with more pericytes
- Artery: three thick layers, so can get through endothelium but can’t go through other layers –> atherosclerosis
What is the consequence of increased vascular permeability?
- Leakage of plasma protein through endothelial junctions into sub-endothelial space
What is found right below the endothelium?
- sticky molecules
= collagens and proteoglycans
How are foam cells formed?
- LDLs go under the endothelial layer when endothelium is activated
- stuck in sub endothelium because of sticky proteins
- oxidised in oxidative environment
- macrophages phagocytose oxidised LDLs
- forms foam cells
What is the significance of foam cells?
Source of chronic inflammation
What are the two different types of flow? Briefly describe them
- Laminar flow
- streamlined
- outermost layer moves slowest, innermost moves fastest
- platelets carried in centre - Turbulent flow
- Interrupted
- Rate of flow exceeds critical velocity
- when fluid passes a contraction, sharp turn or rough surface
Why does atherosclerosis occur at branch points?
You get turbulent flow at branch points
Laminar flow= detected by endothelium as +ve protective signal but turbulent = opposite
What does laminar flow promote?
- anti- thrombotic, anti- inflammatory factors
- endothelial survival
- NO production
- Inhibition of SMC proliferation
What does turbulent blood flow promote?
- coagulation
- leukocyte adhesion
- SMC proliferation
- endothelial apoptosis
- loss of NO production
