Atheroma Flashcards
what is the initiating factor in atheroma?
most likely some form of damage to the endothelium
- the damaged lining of blood vessel allows for the movement and uptake of __ from the ____ into the _____ of the artery. It is not the LDLs themselves that causes atheromatous deposits, it is when the LDL are _____ to ____ that they cause atheroma
the damaged lining of blood vessel allows for the movement and uptake of LDL from the blood into the intima of the artery. It is not the LDLs themselves that causes atheromatous deposits, it is when the LDL are oxidised to OXLDL that they cause atheroma
what does endothelial dysfunction lead to? 4 things
Increased permeability
Monocyte adhesion
Monocyte emigration
Platelet adhesion
2.Migration of _____ across the endothelium into the intima where they become macrophages. Macrophages are known for their _____ properties but in the intima of the artery they do something different.
Migration of monocytes across the endothelium into the intima where they become macrophages. Macrophages are known for their scavenging properties but in the intima of the artery they do something different.
what are the roles of macrophages in atherosclerosis ? 4 things
- Generation of reactive oxygen species
- Production of cytokines
- Production of growth factors
- uptake of OXLDL
what does the generation of ROS by macrophages do?
Generation of reactive oxygen species leading to oxidation of lipoproteins
what does the production of cytokines by the macrophages do?
Production of cytokines which promote chemotaxis and adhesion of further leucocytes
what does the production of growth factors do?
Production of growth factors contributing to smooth muscle proliferation
Lipoprotein Oxidation means that they:
- more easily i______ by macrophages
- act as ___ ___ for monocytes
- increase monocyte ______
- inhibit _____ motility, trapping macrophages within the _____
- stimulate ___ and ______ ____ release
- directly damage ____ and s___ ____ cells
- induce an _____ response
Lipoprotein Oxidation
- more easily ingested by macrophages
- act as chemotactic factors for monocytes
- increase monocyte adhesion
- inhibit macrophage motility, trapping macrophages within the plaque
- stimulate cytokine and growth factor release
- directly damage endothelial and smooth muscle cells
- induce an antibody response
- Uptake of OXLDL by ____ (using _____ receptors) converts them to cholesterol-laden _____ cells that form a ____ ____ (an early event in atherogenesis)
Uptake of OXLDL by macrophages (using scavenger receptors) converts them to cholesterol-laden foam cells that form a fatty streak (an early event in atherogenesis)
is the fatty streak reversible?
somewhat if the level of blood cholesterol is reduced but once you get the formation of the fibrofatty plaque you get fibrosis
- The lipid laden macrophages in the intima produce molecules like ____ ____ ____- 1 - this leads to increased accumulation of____
The lipid laden macrophages in the intima produce molecules like macrophage chemotactic protein - 1 - this leads to increased accumulation of macrophages
- If the disease progresses we get the formation and release of ___ _____ which change the histology of the blood vessels - causing division and _____ of ___ ____ cells in the intima by the molecule ____. _____ is produced by platelets and i____cells. Also get the deposition of ______ and ______ by myofibroblasts. The ____ and things are the scar tissue components - this is non-elastic and increases the shear stress which increases the damage to the endothelium.
If the disease progresses we get the formation and release of inflammatory mediators which change the histology of the blood vessels - causing division and proliferation of smooth muscle cells in the intima by the molecule PGDF. PGDF is produced by platelets and inflammatory cells. Also get the deposition of collagen and fibronectin by myofibroblasts. The collagen and things are the scar tissue components - this is non-elastic and increases the shear stress which increases the damage to the endothelium.
The formation of an atheromatous plaque consisting of a lipid core (product of _____) and a fibrous cap (______ cells and ______ tissue)
The formation of an atheromatous plaque consisting of a lipid core (product of dead foam cells) and a fibrous cap (smooth muscle cells and connective tissue)
The fibrosis means that the vessel has lost its elascticity, what does this do?
creates even more turbulent flow and more endothelial damage - This creates a positive circle
