Vascular Endothelium Flashcards
Define atherosclerosis.
Chronic inflammatory disease of the arteries
What are the three layers of blood vessel walls and what is contained in each layer?
Tunica intima - endothelial cells
Tunica media - smooth muscle cells
Tunica adventitia - vasa vasorum and nerves
What is the process by which endothelial cells know that they need to form a single layer?
Contact inhibition
State some roles of the endothelial cells.
Angiogenesis
Vascular tone and permeability
Thrombosis and haemostasis
Where does leukocyte recruitment normally take place? Why does this normal recruitment of leukocytes not cause atherosclerosis?
Post-capillary venules
Normally, the leukocytes will pass through the endothelium and digest the basement membrane and pass through to the tissues
How are the large vessels different to the post-capillary venules?
Beyond the endothelium there is a THICK layer which the leukocytes cannot get through so they get stuck in the sticky subendothelial space.
Briefly describe leukocyte recruitment.
Leukocytes have weak interactions via selectins. When the endothelium is activated, it will express chemokines that bind to receptors on the leukocytes and switches their integrins to the high affinity state and subsequent binding to its ligand on the endothelial cells. This allows leukocyte immobilisation on the endothelial surface and transmigration.
Describe the sequence of events starting from endothelial activation and ending with atherosclerosis.
Endothelial activation –> LDL infiltration –> oxidation of LDLs –> LDLs get stuck in the sticky subendothelial layer (consisting of collagen and proteoglycans) –> macrophages infiltrate –> macrophages phagocytose the LDLs and form foam cells –> foam cells accumulate and form fatty streaks
Where does atherosclerosis tend to occur?
Branching points of arteries
How does blood flow affect the endothelium?
Laminar flow gives a positive protective signal to the endothelium so the endothelium is in an anti-inflammatory and anti-thrombotic state (NO is produced). Promotes endothelial survival.
Turbulent flow switches the balance and makes the endothelium pro-thrombotic and pro-inflammatory. Promotes endothelial apoptosis.
What is angiogenesis?
The formation of new blood vessels by sprouting from pre-existing vessels.
What triggers angiogenesis?
Hypoxia
Why is angiogenesis, in the context of cardiovascular disease, related to the Janus paradox?
Angiogenesis is bad for atherosclerosis - angiogenesis is stimulated from the vasa vasorum which become fragile and allow more LDLs in
Angiogenesis is good for myocardial infarction - therapeutic angiogenesis could reoxygenate ischaemic tissue downstream of an occlusion
What is cell senescence?
Growth arrest that halts the proliferation of ageing and/or damaged cells
This is protective against cancer because it prevents damaged cells from proliferating
What is the problem with cell senescence?
Senescent cells can develop a pro-inflammatory phenotype
