Vascular Endothelium in Cardiovascular disease Flashcards
Where do most endothelial cells reside?
98% of all endothelial cells reside within the microvasculature.
What are the 3 layers of blood vessels?
Tunica adventitia - Vasa vasorum ,nerves
Tunica Media - Smooth muscle cells
Tunica Intima - Endothelium
What are capillaries made up of?
Endothelial cells & pericytes
What is the role of the Microvascular Endothelium?
It is the source of angiocrine factors that maintain tissue homeostasis & organ regeneration.
What diseases can dysfunctional endothelium contribute to ?
Ischemia
Chronic inflammatory disease
Cancer
Diabetes
What are organotypic properties?
Endothelial cells have tissue specific properties & expression profiles. Heterogenous.
How deep are endothelial cells?
Monolayer - 1 cell deep
What is the role of the endothelium?
Barrier separating blood from tissues
Very extensive >1000m2, >100g
Very flat cells
What is Contact inhibition?
Formation of endothelial cell junctions, resulting in cells saying to each other stop growing.
What is the life span of endothelial cells?
Endothelial cells have a long life & low proliferation rate, unless there is damage.
What are some essential functions of blood vessels controlled by endothelial cells?
Vascular tone Aniogenesis Haemostasis & thrombosis Permeability Inflammation
What is Angiogenesis?
Formation of new blood vessels.
What pathways are activated when endothelial cells are resting?
Anti-Inflammatory
Anti-thrombotic
Anti-proliferative
What pathways are activated when endothelial cells are activated?
Pro-inflammatory
Pro thrombotic
Pro-Angiogenic
What triggers chronic activation of the endothelium?
Smoking Viruses Mechanical stress Inflammation High Blood pressure OxDl High Glucose
What does Chronic activation of the endothelium result in over time?
Thrombosis Senescence Permeability Leukocyte recruitment ALL contribute to the development of atherosclerosis.
What is the Pathogenesis of Atherosclerosis?
Initial injury results in activation of the endothelium.
This causes an increase in; Endothelial permeability, systems which promote adhesion & migration of leukocytes. This results in leukocyte accumulation in sub-endothelial space. Phagocytosis of the lipids there causes Foam-cell formation.
Formation o an advanced complicated lesion of atherosclerosis.
What does the formation of an advanced complicated lesion of Atherosclerosis consist of?
Macrophage accumulation
Formation of Necrotic core
Fibrous Cap formation
Angiogenesis
What are some stimuli & risk factors for Endothelial cell dysfunction in Atherogenesis?
Hypercholesterolaemia Diabetes mellitus Hypertension Ageing Oxidative stress Proinflammatory cytokines
What allows the Leukocyte adhesion cascade?
Inflammatory agents activate endothelium to express molecules that support this process.
What is the difference in structure between Capillaries & Post-capillary venules?
PCV have more pericytes
When does the recruitment of blood leukocytes into tissues normally take place?
During inflammation;
Leukocytes adhere to the endothelium of the post-capillary venules and transmigrate into tissues.
What is different about the recruitment of blood leukocytes in atherosclerosis?
Leukocytes adhere to activated endothelium of large arteries and get stuck in the sub-endothelial space
What is the role of Monocytes in Atherosclerosis?
Migrate into the sub-endothelial space, differentiate into macrophages and become foam cells.
What does increased vascular permeability lead to?
Leakage of plasma proteins through the junctions into the sub-endothelial space.
How does vascular permeability lead to atherosclerosis?
Lipoproteins come through leaky junctions and bind proteoglycans. They get oxidated in the sub-endothelial space (good environment for oxidation). Macrophages englobate Lipoproteins to form Foam cell.
What are the three stages in the development of Atherosclerosis?
1 - Endothelial cell dysfunction
2 - Fatty streak Formation
3 - Atherosclerosis lesion formation
Where do atherosclerosis plaques preferentially occur?
Bifurcations and curvatures of the vascular tree
Where is blood flow laminar?
Straight parts of the arterial tree.
Wall shear stress is high and directional
Where is blood flow Disturbed?
Branches & Curvatures.
Non-uniform & 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 present?
Thrombosis, inflammation (leukocyte adhesion)
endothelial apoptosis
SMC proliferation
Loss of Nitric oxide (NO) production
Why is NO essential for the health of the Cardiovascular system?
It; Dilates blood vessels Inhibits monocyte adhesion Reduces platelet activation Reduces proliferation of SMC in the vessel wall Reduces release of superoxide radicals Reduces oxidation of LDL Cholesterol
What is Angiogenesis essential for?
Embryonic development
Menstrual cycle
Wound Healing
Why is Angiogenesis two-faced?
It promotes plaque growth but prevents damage post iscchaemia.
What are circulating endothelial cells a marker of in Covid-19?
Severe injury, levels can be corrected by anticoagulation. Covid has been proposed as a disease of endothelial cell dysfunction
What leads to thromboinflammation?
loss of the normal antithrombotic and anti-inflammatory functions of endothelial cells causes thrombosis with associated inflammation.
What is the cascade between covid infection and Procoagulation?
Covid infection
Cytokine storm
Endothelial activation
Procoagulant switch
