Vascular Endothelium Flashcards
Describe the basic structure of vascular endothelium
Outermost layer is tunica adventitia containing vasa vasorum and nerves. Middle layer is tunica media covered in external and internal elastic membranes containing smooth muscle cells. The innermost layer is tunica intima contains lamina propria (smooth muscle and connective tissue) and basement membrane coating endothelium.
How are capillaries formed and what is their role?
Capillaries and venules are formed only by endothelium, supported by some mural cells (pericytes) and a basement membrane. Capillaries is where the exchanges of nutrients and oxygen between blood and tissues occur. Microvascular endothelium promotes tissue homeostasis - damage to endothelium can cause organ dysfunction.
What is a role of microvascular endothelium?
Microvascular endothelium is the source of angiocrine factors required for the maintenance of tissue homeostasis and organ regeneration.
What is tissue specific microvasculature?
Endothelial cells and microvasculature have organotypic (tissue-specific) properties and expression profiles.
What are the types of endothelium?
Non-fenestrated: Found in muscle, lung, skin, blood brain barrier
Fenestrated: Kidney glomerulus, gastrointestinal tract
Discontinuous: Liver, marrow sinus
Describe the organisation and role of endothelial cells
The Endothelium acts as a vital barrier separating blood from tissues. Endothelial cells are very flat, about 1-2 µm thick and 10-20 µm in diameter. Formed by a monolayer of endothelial cells, one cell deep (contact inhibition). Live a long life and have a low proliferation rate (unless new vessels are required: angiogenesis).
Endothelial cell regulate essential functions of blood vessels.
How does contact inhibition work?
Contact inhibition is essentially when endothelial cell-cell junction formation provides a signal to the cells halting growth.
What functions of blood vessels and tissues does the endothelium control?
- Tissue homeostasis and regeneration
- Permeability
- Inflammation
- Haemostasis & Thrombosis
- Angiogenesis
- Vascular tone
PHAVIT
What factors activate the endothelium?
Smoking, Viruses, Mechanical stress, Inflammation, High blood pressure, OxLDL, High glucose
HOVHIMS
What are 4 outcomes of an activated endothelium?
Thrombosis, Senescence, Permeability, Leukocyte recruitment. Lead to atherosclerosis.
What is the first step of atherosclerosis?
Endothelial Dysfunction in Atherosclerosis. The earliest changes that precede the formation of lesions of atherosclerosis take place in the endothelium. These changes include:
- Increased endothelial permeability to lipoproteins and other plasma constituents mediated by nitric oxide, prostacyclin, platelet-derived growth factor, angiotensin II, and endothelin
- Up-regulation of leukocyte adhesion molecules, including L-selectin, integrins, and platelet–endothelial-cell adhesion molecule 1
- Up-regulation of endothelial adhesion molecules, which include E-selectin, P-selectin, intercellular adhesion molecule 1, and vascular-cell adhesion molecule 1;
- Migration of leukocytes into the artery wall, which is mediated by oxidized low-density lipoprotein, monocyte chemotactic protein 1, interleukin-8, platelet-derived growth factor, macrophage colony-stimulating factor, and osteopontin.
What are the 5 stimuli for endothelial cell dysfunction in atherogenesis?
- Hypercholesterolaemia (e.g. oxidatively modified lipoproteins)
- Diabetes mellitus / metabolic syndrome
- Hypertension (e.g. ANG-II & ROS)
- Sex hormonal imbalance (e.g. oestrogen deficiency & menopause)
- Ageing
What are the 5 risk factors for endothelial cell dysfunction in atherogenesis?
- Oxidative stress
- Proinflammatory cytokines (e.g. IL-I & TNF)
- Infectious agents (e.g. bacterial endotoxins & viruses)
- Environmental toxins (e.g. cigarette smoke and air pollutants)
- Haemodynamic forces (e.g. disturbed blood flow)
Describe the leukocyte adhesion cascade?
- Capture via endothelial cells
- Activation: rolling of leukocyte, slow rolling and finally arrest
- Adhesion, strengthening, spreading
- Intravascular crawling
- Paracellular and transcellular transmigration)
How does leukocyte recruitment change in atherosclerosis?
Recruitment of blood leukocytes into tissues normally takes place during inflammation: leukocyte adhere to the endothelium of post-capillary venules and transmigrate into tissues. In atherosclerosis, leukocytes adhere to activated endothelium of large arteries and get stuck in the subendothelial space. Monocytes migrate into the subendothelial space, differentiate into macrophages and become foam cells.
