The endothelium Flashcards
What is the leukocyte adhesion cascade?
Capture, Rolling - selectins
Arrest, spreading - integrins
Paracellular crawling
Transmigration/Diapedesis
What are the leukocyte adhesion deficiencies?
1: no CD18 integrin
2: no selectin
3: no integrin activation
What is the result of LADs?
recurrent infections
What is the function of the endothelium?
Lines the lumen of blood vessels
Provides protection from contents
Mediates cell-ECM and cell-cell interactions for immune and physiological responses
What is the structure of the endothelial receptors?
Glycoproteins/Glycolipids with internal enzymatic activity
How does the epithelium for a tightly linked layer?
Ca dependant cadherin interactions
How are blood vessels produced?
Vasculogenesis is de novo synthesis
Angiogenesis mediates tissue growth
How is angiogenesis hijacked by cancer?
Hypoxia causes HIF-1α TF to produce growth factors
VEGFr activation causes epithelium to migrate and proliferate
What is neovascularisation?
Leaky blood vessels provide tumour with nutrients and allow metastases
Which drugs can be used to target angiogenesis in cancer?
Sutent and Avastin block receptors
What are the examples of epithelial receptors?
vEGFr 1-3
Neuropilin 1,2
HSPG
How is atherosclerosis caused?
Macrophages (leukocyte derived monocytes) and LDLs as foam cells accumulate in lesions under epithelium
Rupture causes clotting/thrombosis
How does endothelium act to reduce thrombosis?
NO synthases block clotting and leukocyte adhesion
NO causes smooth muscle to produce cGMP for vasodilation
How does Kaposi’s sarcoma herpes virus target epithelium?
Uses vGPCRs to stimulate proliferation and block apoptosis in epithelium
Lytic cycle induces angiogenesis
