Vascular Endothelium 2 Flashcards
Describe the endothelium of the blood vessels
Single cell layer
Lots of gap junctions for cell-cell communication
What are the three layers of the blood vessels (outside->inside)
Tunica adventitia (vasa vasorum, nerves) Tunica media (smooth muscle cells) Tunica intima (lamina propria, basement membrane, endothelium)
What can endothelium dysfunction lead to
Atherosclerosis
Fatty streak formation and therefore advanced complicate lesion
Describe the microcirculation
Endothelial cells surrounded by basement membrane and pericapillary cells
Post-capillary venues - more pericytes
What are the functions of the endothelium
Angiogenesis e.g. matrix products and growth factors
Thrombosis & haemostasis e.g. procoagulant factors and antithrombotic factors
Inflammation e.g. Adhesion molecules and inflammatory mediators
Vascular tone permeability e.g. vasoconstricting factors and vasodilator factors
Describe leukocyte recruitment in inflammation
Blood leukocytes are recruited into tissues where they adhere to the post-capillary venule endothelium
Describe leukocyte recruitment in atherosclerosis
Leukocytes adhere to activated endothelium if large arteries and get stuck in the sub endothelial space (monocytes -> macrophages)
What role does angiogenesis play in leukocyte recruitment
Newly formed post-capillary venules at the base of the developing lesions provide a further portal for leukocyte entry
Explain the leukocyte adhesion cascade
- Inflammatory trigger activates the endothelium to express more adhesion molecules
- Leukocytes roll along the endothelium
- Leukocytes bind to the adhesion molecules
- Leukocytes stop
- Leukocyte passes through the endothelium through small junctions
What causes cells to become quiscent
When two dividing cells touch each other, they engage with molecular pathways which cause them to become quiescent.
Endothelial cells rarely divide (not for repair). Therefore they form a monolayer
What is an important junction in vascular endothelium
VE-cadherin is a very important junction
Describe the permeability of the vascular endothelium
Regulates flux of fluid and molecules from blood to tissues and vice versa
Increased permeability -> leakage of proteins through junctions
Describe the changes in permeability which lead to atherosclerosis
Endothelial dysfunction causes an increase in permeability
Activated LDLs pass through and bind to proteoglycans
Oxidation and phagocytosis by macrophages form foam cells
Why does atherosclerosis often occur at branch points
Laminar and turbulent flow
Describe laminar flow
Streamlined, outermost layer moves the slowest
Promotes antithrombotic factors, anti-inflammatory factors, NO production and inhibition of SMC proliferation (protective function)
Activates KLF2 and KLF4
