Lecture 1 - atherosclerosis Flashcards
what is atherosclerosis
deposition of cholesterol under endothelial cells
what causes a thrombotic event
lesion rupturing -> contents of the plaque enter the bloodstream and platelets will recognise that as something foreign; causing a clot or thrombotic event. necrosis occurs due to a blocked artery - supply of O2 and nutrients downstream of blockage is blocked
what does endothelial dysfunction cause
reduced NO. NO is an anti-inflammatory in the body
sterile inflammation
no pathogens; tissue attacking on itself
statins
increase in anti-inflammatory. reduce mortality by up to 40%. overtime became more and more synthesis - upregulate LDL receptors to reduce the synthesis and secretion of lipoproteins from the liver
PCSK9 inhibitors
lead to a lack of binding with LDL receptors, hence lowering LDL receptors’ degradation.
PCSK9 protein binds to LDL receptor and drives its degradation - blocks this by monoclonal antibody -> more LDL receptor on the surface so more LDL can be taken up from the bloodstream
statins (2)
inhibits HMG-CoA reductase (a rate limiting enzyme in hepatic cholesterol biosynthesis) - leads to upregulation of LDL receptors in liver and increased removal of Apo B-containing lipoproteins from the circulation, reduction in synthesis and secretion of lipoproteins from the liver, anti-inflammatory action, enhanced DNA repair and reduced senescence in vascular smooth muscle cells
other drugs used in combination with statins
Anti-platelet medications, beta blocker medications, ACE inhibitors, CCBs, diuretics
CANTOS trial
Canakinumab Anti-inflammatory Thrombosis Outcomes Study - 3.7 year follow up. 150mg of canakinumab every 3 months led to lower rate of recurrent cardiovascular events than placebo
15% reduction in non-fatal MI, non-fatal stroke, CVD death
30% reduction in ever needing bypass surgery or angioplasty
