Atherosclerosis

Question 1

What are the differences between arteriosclerosis and atherosclerosis?

Answer 1

Arteriosclerosis is when we get narrowing and stiffening of the arteries - reduces blood flow
Atherosclerosis is when we get formation of plaques (containing lipids) potentially leading to blood clots

Question 2

What are the risk factors of atherosclerosis?

Answer 2

Obesity
High cholesterol diet (LDL)
Hypertension
Diabetes
Smoking
Alchohol

Question 3

What are the clinical complications of atherosclerosis?

Answer 3

Brain - Carotid artery - Stoke/TIA
Heart - Coronary artery - acute coronary syndromes - stable plaque - angina - unstable plaque - Acute coronary syndromes - unstable angina, STEMI/NSTEMI
Kidney - Renal artery - kidney disease
Testicles - erectile dysfunction
Legs/arms - PAD

Question 4

What are the methods of diagnosing AS?

Answer 4

Medical history, physical examination
Whooshing sound 
Blood test - abnormal high lipids in blood
Stress test
Weak pulse in arm/leg

Question 5

What are the steps in atherogenesis?

Answer 5

1) Endothelial Cell Injury - toxins (cigarette smoke, hypertension, high LDL, high glucose) causes damage to the endothelial cells in the artery
2) LDL crosses the cells and enters the tunica intima - oxidised by ROS/MMPs (trapped now) and activates endothelial cells - causes them to express adhesion molecules (ICAM1/e/p-selectin) - recruits monocytes - monocytes move into the tunica intima and are differentiated into macrophages (aided by T cells -Th17). Macrophages ingest LDL and become foam cells (fatty streak). Foam cells release chemokine to recruit more macrophages. Release IGF-1 to recruit SM cells from the tunica media to the tunica intima and SM proliferation causes increase in collagen which hardens the plaque.
3) Foam cells die and release lipids and DNA which attracts neutrophils - also release pro inflammatory cytokines and ROS which promotes inflammation. Caused by hypoxia leading to apoptosis of foam cells. Plaque contains foam cells, dead foam cells, lipids, SM, macrophages, neutrophils
4) Plaque grows in time over many year - fibrous cap - thrombus can form on top of plaque - if thrombus breaks free forms an embolus

Question 6

How do we measure endothelial function?

Answer 6

FMD (Flow mediated dilation) - non invasive - measure ability of brachial artery to respond with endothelial NO during reactive hyperaemia after 5 mins occlusion - measure vasodilation using ultrasound - extensive preparation: no smoking, fasting, quiet, no exercise before

Question 7

What diet changes can we make to prevent the risk of atherosclerosis?

Answer 7

Reduce cholesterol in our diet: avocado, oats, brussel sprouts, beans, sweet potato

Question 8

How can we modify LDL pharmacologically?

Answer 8

Statins (e.g Lipitor) - reduce produce of LDL cholesterol by the liver. Inhibit HMG CoA reductase which converts acetate to cholesterol. Must combine with a low LDL diet

Ezetimibe - prevents Small Intestine absorbing cholesterol - combine with statins

PCSK9 inhibitors - e.g. Evolucumab - prevents PCSK9 degradation of LDL receptors on liver - reduces LDL-C from the blood