Cardiovascular Systems 9 - Vascular Endothelium 2 Flashcards
Describe the basic structure of blood vessels.
- There are three layers
- The top layer is the tunica adventitia (vasavasorum, nerves)
- Tunica media below (smooth muscle cells)
- Tunica intima is the inner layer, containing the endothelium
List the stimuli of endothelial cell dysfunction, resulting in atherogenesis.
- Oxidative stress
- Proinflammatory cytokines
- Infectious agents
- Environmental toxins
- Disturbed blood flow
- Hypercholesterolaemia
- Diabetes mellits
- Hypertension
Describe the process of leukocyte recruitment in atherosclerosis.
- Leukocytes adhere to activated endothelium of large arteries and get trapped in the sub-endothelial space
- This occurs as activation of the endothelium stimulates the expression of receptors
- Leukocytes also enter at post-capillary venules
- Monocytes migrate into the sub-endothelial space forming macrophages
What is the difference between the capillary and the post-capillary venules?
- Capillaries consist of endothelial cells surrounded by a basement membrane and pericapillary cells (pericytes)
- Post-capillary venules have a similar structure but with more pericytes
Describe the process of lipoprotein trapping in atherosclerosis formation
- Activated endothelial cells have high permeability and allow the lipoproteins to diffuse across the endothelium
- They encounter proteoglycans and are oxidated
- Macrophages then engulf all of the lipoproteins and form a foam cell
- Forms fatty streaks
Why does aterosclerosis happen at branch points?
- There is a difference in blood flow
- Laminar flow occurs in vessels with a constant diameter, while turbulent flow occurs at branch points due to bends and narrowings.
- Turbulent flow promotes coagulation, leukocyte adhesion, and reduced NO production.
List the positive effects of nitric oxide on the vascular endothelium.
- Dilates blood vessels
- Reduces LDL oxidation
- Reduces platelet activation
- Inhibits monocyte adhesion
- Reduces proliferation of smooth muscle cells in atherosclerosis
- Reduces release of superoxide radicals
What transcription factor is present in the atherosclerosis susceptible region?
NF kappa B (activates cytokine production, and is proinflammatory)
List the three key epigenetic mechanisms.
- DNA methylation
- Histone modification
- miRNA
Why is the study of epigenetics important in atherosclerosis?
As epigenetics could be targeted by drugs
How does stable flow prevent atherosclerosis?
- Downregulates expression of DNA methyltransferases
- This ensures antiatherogenic genes, such as KIf4 and HoxA5 remain demethylated, enabling their expression
How does disturbed flow increase atherosclerosis?
- Increases expression of DNA methyltransferases
- Results in hypermethylation of antiatherogenic genes, like KIf4 and HoxA5
- This reduces their expression
What is angiogenesis?
The formation of new vessels by sprouting from existing vessels
What processes are angiogenesis essential for?
- Embryonic development
- Menstrual cycle
- Wound healing
What are the pros and cons of angiogenesis?
- It prevents damage after ischaemia
- However, it promotes growth of plaque
