Progression And Regression Of Experimental Atherosclerotic Lesions In The Presence Or Absence Of High LDL Levels Flashcards
What did Anitschkow’s hypothesis claim?
That hypercholestrolemia is the major potential causative agent of atherosclerosis
Which animal model did Anitsckow use to test his hypothesis
LDL receptor and APOBEC1 double knockout mice (hence these mice had severe familial hypercholesterolemia)
He also used regular mice with high LDL intake diets - which had similar outcomes
What role does the LDL pathway play in the body?
A major role in delivering cholesterol to the cells of the body
Why do arterial lesions develope when LDL levels are raised?
LDLs are able to cross the endothelium to the subendothelial space and start the events that lead to the lesion;
Endothelial cells and macrophages are able to oxidise LDL particles, these modified particles cannot be uptaken by physiological LDL receptors, and accumulate in the subendothelial space
What happens to modified LDL particles in the subendothelial space?
They are uptaken by scavenger receptors on macrophages (which eventually become foam cells). These receptors are not switched off like physiological LDL receptors , so they continue to uptake LDLs until the cell dies - lipid laden cells
What happens to dead foam cells?
They give rise to the extracellular lipid that rearranges itself. Lipid molecules cluster together, interspesed with matrix components, cell debris etc.
What are statins
Drugs used to lower cholesterol levels by competitively inhibiting HMG Co-A reductase, thus inhibiting cholesterol synthesis.
How effective are statins?
They are extremely effective in reducing circulating LDL levels (30-40%) and they dramatically reduce the risk of coronary heart disease
