VASCULAR ENDOTHELIUM Flashcards
What are the 3 layers of blood vessels?
Excluding capillaries and venules
Tunica adventitia - vasa vasorum, nerves
Tunica media - smooth muscle cells
Tunica intima - endothelium
What is the structure of a capillary?
Formed only by endothelium supported by mural cells (pericytes) and a basement membrane
Why is microvascular endothelium so important?
Source of angiocrine factors needed for tissue homeostasis and organ regeneration
Where is non-fenestrated microvasculature seen?
muscle, lung, skin, BBB
Where is fenestrated microvasculature seen?
Kidney gomerulus
GI tracy
Where is discontinuous microvasculature seen?
Liver
Marrow sinus
What are the dimensions of an endothelial cell?
1-2 um thick
10-20 um in diameter
How do endothelial cells form a flat monolayer?
Via contact inhibition where endothelial cell-cell junctions are formed. Once formed this signals the cells to stop growing
What functions of the blood vessels and tissues does the endothelium control?
Vascular tone Angiogenesis Permeability Inflammation Haemostasis and thrombosis
How do the endothelial cells control thrombosis and haemostasis?
Procoagulant factors (VWF, thromboxane A2...) Antithrombotic factors (prostacyclin, antithrombin...)
How do the endothelial cells control angiogenesis?
Matrix products (fibronectin, laminin, collagen...) Growth factors (IGF, TGF, colony stimulating factor)
How do the endothelial cells control inflammation?
Inflammatory mediators (IL 1/6/8, leukotrienes, MHC II) Adhesion molecules (ICAMs, VCAM, selectins)
How do the endothelial cells control vascular tone and permeability?
Vasoconstricting factors (ACE, thromboxane A2...) Vasodilating factors (nitric oxide, prostacyclin)
What are the two sides of endothelial homeostasis?
Resting endothelium:
- anti-inflammatory
- anti-thrombotic
- anti-proliferative
Activated endothelium:
- pro-inflammatory
- pro-thrombotic
- pro-angiogenic
List the factors which can cause activation of the endothelium
Mechanical stress Inflammation High blood pressure OxLDL Highe glucose Viruses Smoking
What does chronic activation of the endothelium lead to?
Atherosclerosis
What does activated endothelium cause?
Thrombosis
Senesence
Leukocyte recruitment
Permeability
Outline the pathogenesis of atherosclerosis
- Endothelial dysfunction causing leukocyte migration and adhesion into the sub-endothelial spaces
- Fatty streak/foam cell formation
- Formation of advanced, complicated lesion of atherosclerosis
What are the stimuli and risk factors for atherogenesis?
Hypercholesterolaemia
Diabetes mellitus/metabolic syndrome
Hypertension
Sex hormonal imbalance (oestrogen def, menopause)
Ageing (endothelial cell senescence and inflammation)
Oxidative stress
Pro inflammatory cytokines
Infectious agents
Environmental toxins
Haemodynamic forces (disturbed blood flow)
What are the mechanisms in the pathogenesis of atherosclerosis?
Leukocyte recruitment
Permeability
Shear stress
Angiogenesis
Where does leukocyte adhesion and migration usually occur?
Post-capillary venule and transmigrated into tissues
What are post-capillary venules?
Structure similar to capillaries but have more pericytes
What normally occurs in the transmigration of leukocytes into tissues compared to what occurs in atherosclerosis?
Transmigration via paracellular or transcellular in post capillary venules then chews up basement membrane to get to tissue
In atherosclerosis, leukocytes adhere to activated endothelium which are expressing markers in LARGE ARTERIES. When they squeeze through the endothelium they are instead presented with the thick walls of the artery and become stuck in subendothelial space
How are foam cells in atherosclerosis formed and what does this promote?
Monocytes migrate into the subendothelial space and differentiate into macrophages and become foam cells promoting the formation of plaque
