Vascular Endothelium 2 Flashcards
What happens during the leukocyte adhesion cascade?
- First start to roll along the endothelium and they spread and eventually find junctions to get through
- This happens because the inflammatory agents have activated the endothelium to express molecules that support this process
What does recruitment of blood leukocytes into tissues normally take place?
during inflammation
Where do the leukocytes adhere to?
endothelium of post-capillary venules and transmigrate into tissues
What is a capillary?
endothelial cells surrounded by basement membrane and pericapillary cells (pericytes)
What is a post-capillary venule?
structure similar to capillaries but more pericytes
How are capullary venules formed?
- by basically single endothelial cells within a few perictyes and basement membrane
- So leukocytes can squeeze through the junctions
What sort of arteries activated endothelium do leukocytes adhere to? What happens?
- adhere to activated endothelium of large arteries 2. get stuck in the subendothelial space
Where do monocytes migrate to and what happens to them?
- migrate into the subendothelial space
2. differentiate into macrophages and become foam cells
What does the endothelium regulate?
flux of fluids and molecules from blood to tissues and vice versa
Where do Atherosclerotic plaques occur?
preferentially at bifurcations and curvatures of the vascular tree
Why do atheroscelrotic plaques occur there?
low patterns and hemodynamic forces are not uniform in the vascular system
What is blood flow like in straight parts of the arterial tree?
- blood flow is laminar
2. wall shear stress is high and directional
What is blood flow like in branches and curvatures?
- blood flow is disturbed
2. nonuniform and irregular distribution of low wall shear stress.
What does laminar blood flow promote?
- anti-thrombotic, anti-inflammatory factors
- endothelial survival
- Inhibition of SMC proliferation
- Nitric oxide (NO) production
What does disturbed blood flow promote?
- Thrombosis, inflammation (leukocyte adhesion)
- endothelial apoptosis
- SMC proliferation
- Loss of Nitric oxide (NO) production
What does nitric oxide to for the cardiovascular system?
- Dilates blood vessels
- Reduces platelet activation
- Inhibits monocyte adhesion
- Reduces proliferation of SMC in vessel wall
- Reduces release of superoxide radicals
- Reduces oxidation of LDL cholesterol (major component of plaque)
What are the mechanisms in endothelial dysfunction in the pathogenesis of atherosclerosis?
- Leukocyte recruitment
- Permeability
- Shear stress
- Angiogenesis
What is angiogenesis?
Formation of new vessels by sprouting from existing vessels
What is angiogenesis essential for?
- Embryonic development
- Menstrual cycle
- Wound healing
What does angiogenesis promote?
Plaque growth (BAD)
What does therapeutic angiogenesis prevent?
damage post-ischemia (GOOD)
How is permeability controlled?
by endothelial cell-cell junctions
What does increased permeability to lipids contribute to?
early plaque formation
How do leukocytes migrate into tissues?
through post-capillary venules during injury/inflammation
What type of thrombosis is frequent in COVID-19 patients?
- Both venous and arterial thrombi
- Incidence unknown; variability in reports and data analysis
What is coagulopathy?
increased D-Dimers, Fibrinogen
What does coagulopathy correlate to?
poor prognosis (covid-19)
What type of therapy is recommended in all hospitalised COVID-19 patients?
- Anti-thrombotic therapy
- Local, in situ thrombosis points to endothelial role
What are the properties of healthy endothelium?
anti-thrombotic and anti-inflammatory
What does •loss of the normal antithrombotic and anti-inflammatory functions of endothelial cells cause?
thrombosis with associated inflammation: thromboinflammation
What does thromboinflammation happen?
sepsis, ischemia-reperfusion injury etc
What is a theory that causes the endothelial damage secondary to SARS-CoV2?
-cytokine storm (leads to endothelial activation and procoagulant switch)
What does the permeability mean?
-Leukocytes recruitment were leukocytes shouldn’t go
-Lipoproteins through an endothelium that should be tight
So fatty streak formation
When does angiogenesis occur in plaques?
advanced atherosclerotic plaques (late)
What can be found in COVID-19 patients?
circulating endothelial cells
What is another COVID-19 endothelial cell theory?
-SARS-CoV2 enters endothelial cells and causes direct damage
Does SARS-CoV2 actually bind to endothelial cells?
no published evidence
Is there ACE2 expression in endothelial cells?
confusing evidence (on epithelial not endothelial)
