Vascular Endothelium Flashcards
What are the 3 layers of blood vessels?
- tunica adventitia
- tunica media
- tunica intima
What makes up the tunica adventitia?
- vasa vasorum
- nerves
What makes up the tunica media?
- external elastic membrane
- smooth muscle
What makes up the tunica intima?
- internal elastic membrane
- lamina propria
What is the lamina propria?
- smooth muscle
- connective tissue
What are capillaries and venules comprised of?
- endothelium
- pericytes (mural cells)
- basement membrane
What happens at capillaries?
exchange of nutrients and oxygen between blood and tissues
What does the microvascular endothelium do?
a source of angiocrine factors required to promote tissue homeostasis and organ regeneration
What is the impact of a dysfunctional endothelium?
- contributes to disease
- ischemia
- chronic inflammatory diseases
- cancer
- diabetes
- atherosclerosis
Do endothelium cells vary?
yes, they have organotypic properties and expression profiles
What are the properties of endothelial cells in the muscle, lung, skin and blood brain barrier?
continuous non-fenestrated
What are the properties of endothelial cells in the kidney glomerulus, GI tract?
continuous fenestrated
What are the properties of endothelial cells in the liver and marrow?
discontinuous
What are the properties of endothelial cells?
- very flat
- about 1-2 micrometers thick
- about 10-20 micrometers in diameter
What is contact inhibition?
when the junctions of 2 cells join and establishes a junction causing the cells to stop growing
What is the lifespan of endothelial cells?
- long
- low proliferation rate
(unless angiogenesis is necessary)
What are the functions of endotheliun?
- vascular tone
- permeability
- angiogenesis
- haemostasis and thrombosis
- inflammation
What happens when the endothelium is at rest?
promotion of:
- anti-inflammatory
- anti-thrombotic
- anti-proliferative
What happens when the endothelium is activated?
promotion of:
- pro-inflammatory
- pro-thrombotic
- pro-angiogenic
What activates the endothelium?
- smoking
- viruses
- mechanical stress
- inflammation
- high BP
- OxLDL
- high glucose
What happens when there is long term/chronic activation of the endothelium?
- thrombosis
- senescence
- permeability
- leukocyte recruitment
all cause: atherosclerosis
What are the characteristics of endothelial dysfunction in atherosclerosis?
- endothelial permeability
- leukocyte migration
- endothelial adhesion
- leukocyte adhesion
What happens in the fatty-streak formation in atherosclerosis?
- smooth muscle migration
- foam cell formation
- t cell activation
- adherence and aggregation of platelets
- adherence and entry of leukocytes
What happens in the formation of an advanced, complicated lesion of atherosclerosis?
- macrophage accumulation
- formation of a necrotic core
- angiogenesis
- fibrous cap formation
What are the triggers of endothelial dysfunction in atherogenesis?
- oxidative stress
- pro-inflammatory cytokines
- infectious agents
- environmental toxins
- haemodynamic forces
What are the risk factors of endothelial dysfunction causing atherogenesis?
- hypercholesterolaemia
- DM/metabolic syndrome
- hypertension
- sex hormonal imbalance
- ageing
What are the mechanisms that contribute to the development of atherosclerosis?
- leukocyte recruitment
- permeability
- shear stress
- angiogenesis
What happens in the leukocyte adhesion cascade?
- capture
- rolling
- spreading
- between the junctions
When and where does leukocyte recruitment normally occur?
during inflammation, adherence to the post-capillary venules before entering the tissures
What is the structure of a capillary?
- endothelial cells
- basement membrane
- pericapillary cells (pericytes)
What is the difference in the structure of a capillary and a post-capillary venule?
venules have more pericytes (pericapillary cells)
Where does leukocyte recruitment occur in atherosclerosis?
to the activated endothelium of of large arteries and are stuck in the sub-endothelial space
- monocytes differentiate into macrophages and then foam cells
What happens when there is increased permeability of the endothelium?
leakage of plasma proteins through the junctions into the subendothelial space
What happens to blood flow in the straight parts of the arterial tree?
- laminar blood flow
- high an directional wall shear stress
What happens to blood flow in the branches and curvatures of the arterial tree?
- disturbed blood flow
- non-uniform and irregular distribution of low wall shear stress
What does laminar blood flow promote?
- anti-thrombotic, anti-inflammatory factors
- endothelial survival
- inhibitions of SMC proliferation
- NO production
What does disturbed blood flow promote?
- thrombosis, inflammation (leukocyte adhesion)
- endothelial apoptosis
- SMC proliferation
- loss of NO production
What is the role of NO?
key regulator of vascular function
- reduces OxLDL
- vasodilation
- reduces platelet activation
- inhibits monocyte adhesion
- reduces release of superoxide radicals
- reduces SMC proliferation
What is angiogenesis?
formation of new blood vessels by sprouting from existing ones
What is angiogenesis triggered by?
hypoxia
What is angiogenesis essential for?
- embryonic development
- wound healing
- menstrual cycle
What is the double role of angiogenesis?
- promotes plaque growth
if therapeutic: - prevents damage post-ischemia
What is pathological angiogenesis associated with?
advanced atherosclerotic plaques
What is associated with a poor prognosis with a COVID infection?
- increased D-Dimers
- increased fibrinogen
Where are the majority of endothelial cells?
capillaries
What is thromboinflammation?
loss of the normal anti-thrombotic and anti-inflammatory functions of endothelial cells causes thrombosis with associated inflammation
How does covid cause endothelial dysfunction?
- SARS-CoV2 infection
- cytokine storm
- endothelial activation
- procoagulant switch
What are the 2 possible ways that SARS-CoV2 causes endothelial damage?
- cytokine storm secondary to the infection causes the endothelial damage
- SARS-CoV2 enters the cells and causes direct damage (no evidence)
