3.3 Lipid Metabolism + Atherosclerosis

Question 1

Vascular disease is a disease of metabolic disorder (obesity, diabetes etc) and inflammation (smoking, alcohol, infection etc). What can this combination of metabolic disorder and inflammation lead to?

Answer 1

Atherosclerosis

Coronary artery diseases

Hypertension

Question 2

What is atherosclerosis?

Answer 2

Thickening or hardening of arteries caused by buildup of plaque in inner lining

Narrowing of coronary arteries

Question 3

What are the modifiable risk factors for atherosclerosis?

Answer 3

1. Hyperlipidemia
   (LDLs bad, HDLs good)
2. Hypertension
   (BP = 170/95 = 4 fold risk)
3. Current smoking
4. Diabetes mellitus
   (Glycosylation = traps proteins and promotes atherosclerosis)
5. Hyperhomocysteinemia
   (Increased oxidant stress, endothelial dysfunciton, and induction of thrombosis)
6. Infection

Question 4

What is cholesterol and why do we need it?

Answer 4

Cholesterol = sterol molecule

Essential for membrane maintenance + regulating membrane fluidity / permeability

Metabolic precursor of vit D, steroid hormones, and bile salts

Essential for PG2 + thomboxane (platelet aggregation)

Question 5

Where do we get cholesterol from?

Answer 5

Produced throughout the body in all tissues
(highest levels = liver, bone, and spinal cord)

Absorbed from diet

Question 6

Cholesterol is insoluble in the blood, so how is it transported?

Answer 6

Transported as lipoproteins

Enter blood as low-density lipproteins (LDLs)

Returned to liver as high-density lipproteins (HDLs)

Question 7

What are the 4 major lipid classes?

Answer 7

High density
Low density
Very Low density
Chylomicrons

Question 8

What classes of lipid are cholesteryl ester and triglyceride

Answer 8

Cholesteryl ester = High + low density

Triglyceride = Very low density + chylomicrons

Question 9

What are the 3 pathways of cholesterol metabolism?

Answer 9

1. Exogenous (15%)
2. Endogenous (75%)
3. Reverse cholesterol transport

Question 10

How is cholesterol synthesised via the exogenous pathway?

Answer 10

1. Fatty foods digested by pancreatic enzymes into monoglyceride
2. Absorbed by intestinal epithelium
3. Forms into nascent chylomicron and delivered to lymphatic system
4. Transferred to blood stream to provide free fatty acid, triglyceride, and phospholipids to tissue

Question 11

How is cholesterol synthesised via the endogenous pathway?

Answer 11

HMG-CoA mediated production in liver

Mediated by ApoB100

Question 12

How does reverse cholesterol transport work?

Answer 12

HDL ApoAi protein bond to macrophages trhough ABC1 receptor

Collects cholesterol from tissue + transports back to lvier to recycle

Question 13

What are the 3 possible fates of unused cholesterol?

Answer 13

Liver transfers it to bile salt to secrete through bile duct

Accumulate in adipocytes (fat cells)

Excrete through intestine

Question 14

What are 3 causes of acute plaque change in blood vessels?

Answer 14

1. After thrombosis = rupture, fissuring, ulceration
2. Haemorrage = sudden expansion
3. Vasospasm = adrenergic stimuli, stress, platelet production

Question 15

What is the pathogenesis of athersclerosis?

Answer 15

1. Endothelial damage induces inflammatory mediators + clotting
2. Accumulation + oxidation of lipoproteins (mainly LDL) to form fatty streak and initiate monocyte adhesion + migration
3. Intima is invaded by macrophages and T-cells
4. Vascular smooth muscle cells (VSMCs) migrate to intima from media and proliferate
5. Foam cells formed as accumulating lipids are engulfed by VSMCs + macrophages
6. Formation of plaque (fatty, calcified inflammatory plaque with fibrotic capsule)