T3 L16: Atherogenesis Flashcards
In which part of the vessel do atherogenic plaques develop?
In the tunica intima of the artery wall
What causes atherogenesis?
Migration of cells from the tunica media into the tunica intima and caused by recruitment of leukocytes and deposition of lipid from the blood
What are the 3 components of atherogenic plaques?
Cells, matrix components like collagen, and intracellular and extracellular lipids like cholesterol
What 2 effects does NO have on epithelium of vessels?
Vasorelaxation and anti-adhesive properties causing recruitment of monocytes and platelets to be inhibited
Which molecules transform monocytes into macrophages?
Cytokines like IFN-alpha, TNF-alpha, GM-CSF, and M-CSF secreted by the vascular smooth muscle cells
Which molecules attract monocytes to developing plaques?
MCP-1/CCL2, chemokines produced by endothelial cells
What do macrophages produce which can oxidise LDL?
ROS
What role do monocytes have in atherogenesis?
Transform into macrophages which can generate ROS, produce pro-inflammatory cytokines, and express scavenger receptors
What are remnants of LDL?
Smaller lipoproteins
What does oxidised LDL stimulate?
stimulates expression of VCAM-1 and MCP-1`
How do macrophages become foam cells?
When they constantly phagocytose oxidised LDL
What is oxidised LDL recognised by?
Scavenger receptors not LDL receptors
What are vascular smooth muscles cells responsible for?
Structure of the vessel wall
Which cells secrete PDGF and TGF-beta?
Endothelial cells and macrophages
What role do VSMC’s (Vascular smooth muscle cells) have in atherogenesis?
They can differentiate into macrophage-like cells and become foam cells. Activated VSMC’s can synthesise molecules like collagen which deposits in the plaque.
Which 2 types of cells can develop into foam cells?
Macrophages and vascular smooth muscle cells
What is TGF-beta?
Transforming growth factor beta
What can cause epithelial dysfunction/injury?
Hyperlipidaemia, hypertension, smoking, toxins, haemodynamic factors
What is the difference between a stable and ruptured plaque?
Stable plaques have a thick fibrous cap, high VSMC, small amounts of lipid, and few inflammatory cells. Ruptured plaques have a thin fibrous cap, low VSMC content, large lipid content, and many inflammatory cells
What are the 2 main theories behind atherogenesis?
Lipid oxidation and response to injury hypothesis
What is familial hypercholesterolaemia?
A genetic disorder causing elevated levels of LDL
What is the mechanism behind statin action?
They are competitive inhibitors of HMG-CoA reductase
Lovastatin, Compactin, pravastatin, and simvastatin are types of which statin class?
Natural statin
Atorvastatin and Fluvastatin are types of which statin class?
Synthetic statin
What effect does blocking PCSK9 proteins have on cholesterol and why?
Decreased blood cholesterol. PCSK9 proteins degrade LDL receptors so blocking them allows more LDL to enter the liver and therefore leave the blood so it can’t build up in vessels
