Atherogenesis Flashcards
What are the different steps of atherogenesis
normal—>fatty streak—>fibrous plaque—>occlusive atherosclerotic plaque—>plaque rupture
What are the 3 principal components of atherosclerotic plaques
- cells (SMC, macrophages (foam cells) and T cells
- matrix components (collagen, proteoglycans, elastic fibres.
- Intracellular and extracellular lipid (cholesterol and cholesterol esters)
What are two properties of normal endothelium
anti-coagulant and anti-adhesion properties
Early dysfunction of endothelium is functional rather than structural, what are 3 issues due to this.
loss of cell repellant quality allows inflammatory cells into the vascular wall and increased permeability to lipoproteins and all these cause structural damage to the endothelium.
How are monocytes attracted to developing plaques
They are attracted via MCP-1/CCL2 chemokines
What do monocytes do when they enter the arterial wall
They turn into macrophages under the influence of cytokines (TNF-a), secreted by the endothelium and vascular SMC.
What do the macrophages do after they enter the wall
They produce ROS which oxidises LDL in the intima and produces pro-inflammatory cytokines.
How are lipids involved in atherogenesis
LDL’s enter the vascular wall and more easily than other particles, they can be oxidised in the intima which stimulates the expression of VCAM-1 and MCP-1 which directs macrophages to the site of the lesions.
oxidised B-100 binds to scavenger receptors on macrophages and is phagocytosed and foam cells are generated (seen as fatty streaks).
What do foam cells do that is especially bad
they produce inflammatory cytokines which increase the damaging process.
what effect do the cytokines produced by endothelial cells have on VSMC’s?
proliferation and migration into the intima and activated VSMC’s synthesise ECM which deposits in the plaque.
What do statins do
They are competitive inhibitors of HMG-CoA reductase. They are bulky and literally get stuck in the active site. HMG-CoA reductase is used in the process of turning acetyl CoA to cholesterol.
