• To describe the sources of cholesterol in the blood and how it is transported

Dr hughes has edited this transcript so read carefully

cholesterol + triglycerides are transported by VLDL from the hepatocytes in the liver to other places within the body, triglycerides are then released at the target location from the VLDL, when this occurs it becomes LDL which contains high concentrations of cholesterol, at this point (only if the cholesterol is not required anywhere) HDL attaches onto LDL (not quite – apologies if I didn’t explain this well – LDL itself can return to the liver, there’s receptors that can capture it and engulf it back in. HDL transports excess tissue/plasma cholesterol back to the liver. So both are involved in return transport, but elevated LDL levels would indicate you’ve done a lot of transport OUT from the liver initially, if that makes sense, given the VLDL -> LDL link you explain well above) (e.g. from and transports it back into the liver.

if the LDL was left in the circulatory system it would enter (I would say it’s at higher risk of entering) the tunica media of arteries (going through damaged epithelial (endothelial) cells, caused by a variety of factors e.g hypertension – (agree, multiple reasons why this can happen, hypertension itself has multiple causes and can also be the result of atherosclerotic changes as well as causing it depending on the nature of the hypertension itself! More on that in MD3001 tho.) this entering and accumulation alongside interaction (becoming phagocytosed) with macrophages (which also entered the tunica media, as monocytes) can cause macrophages to become ‘’foam cells’’ which themselves attract smooth muscles cells into the tunica media of the artery which ‘’clump’’ together to form fatty streaks which continue to grow as this process continues, eventually narrowing the diameter of the artery so much so that no blood can pass.

• To recognise the association of high blood cholesterol levels with atherosclerosis

^^^^

• To list the drugs used to lower blood cholesterol levels

statins - are drugs that target the HMG-CoA reductase rate limiting step in cholestrol synthesis within the liver

PCSK9 inhibitors - inhibit PCSK9 which causes an increase in the degradation of LDL by the liver.

Bempedoic acid - inhibits ATP citrase lyase which causes decrease in cholestrol synthesis within the liver

Ezetimibe - reduces intestinal uptake/absorption of cholestrol

• To explain the mechanisms of action of these drugs

get rid of bile acid in the intestine by secreting bile acids in the urine

(bile acid sequestrants)

enhance the removal of LDL

(PCSK9 inhibitors)

Inhibit transport protein for cholestrol in the duodenum

(ezetimibe)