12. Atherosclerosis

Question 1

Atherosclerosis

Answer 1

Slow progressive disease (large to medium size muscular elastic arteries) where intimal based plaque develops composed of SMC, inflammatory cells and increased extra cellular matrix

Most frequent and clinically important

Narrowing (stenosis) of blood vessels

Major cause of CVD and peripheral vascular disease

Question 2

Arteriosclerosis

Answer 2

Arterial wall thickening/loss of elasticity

Question 3

Arterioloscleorsis

Answer 3

Affects small arteries and arterioles

Associated with ischemia

Question 4

Structure of atherosclerosis plaques

Answer 4

Fibrous cap: SMC macrophages, foam cells (macrophages engulfing oLDL)

Necrotic center: cell debris, cholesterol crystals, foam cells, calcium

Question 5

Atherosclerotic cardiovascular diseases

Answer 5

Coronary heart disease
Cardiovascular disease
Peripheral artery disease
Aortic atherosclerosis and aneurysm

Question 6

Non modifiable risk factors

Answer 6

Family history
Increasing age
Male gender

Question 7

Modifiable risk factors

Answer 7

Hyperlipidemia - increase of bad LDL cholesterol and decrease in good HDL cholesterol

Hypertension = caused by vasoconstriction - stress on circulation and EC injury

Smoking - decrease NO synthesis therefore increase pro inflammatory cytokines and pro thrombotic (blood clot formation encouraged)

Diabetes - hyperlipidemia with type 2 and excess insulin, insulin decreases bioavailability of NO

Question 8

Pathogenesis

Answer 8

1. EC injury causing increase vascular permeability, leukocyte adhesion
2. Accumulation of lipoproteins (mainly LDL) in vessel wall - become oxidized when moving into intima by ROS
3. Platelets adhesion
4. Monocytes adhesion to endothelium - migration into intima and become macrophages
5. Macrophages injest oxidized LDLs and become foam cells
6. Lipid accumulation increase in inflammatory cytokines
7. SMC recruitment/proliferation and ECM production

Question 9

Response to injury

Answer 9

EC loss results in intima thickening (EC dysfunction)

EC dysfunction caused mostly by
Hemodynamics disturbances
Hyperlipidemia

Question 10

Hemodynamics disturbances

Answer 10

Laminar flow - through vessels except where there is a split, activated endothelial genes whose functions are protective against atheroscleosis

Turbulent flow - flow is obstructed vessel turns or blood flows over rough surface - plaques develop at these branch points and other areas of disturbed blood flow

Question 11

Chylomicrons

Answer 11

Lipoprotein

Deliver triglyceride to cells in the body

Question 12

Very low density lipoprotein (VLDL)

Answer 12

Deliver triglycerides to cells in body

Question 13

Low density (LDL)

Answer 13

Bad cholesterol

Delivers cholesterol from liver to cells in the body

Question 14

High density (HDL)

Answer 14

Good

Reverse cholesterol transport

HDL takes cholesterol from cells back to liver

Question 15

Dyslipoproteins

Answer 15

Increase LDL levels bad

Decrease HDL levels good

Question 16

Chronic hyperlipidemia contributing to atherosclerosis

Answer 16

Excess LDLs travel through tunica intima and become oxidized

oLDLs = when engulfed by macrophages form foam cells, toxic to endothelial cells and SMC, release cytokines and chemokines

Cholesterol crystals = “danger signals” activate innate immunity
In plaques they are dangerous because they can produced DAMP signals (endogenous danger signals)

Question 17

LDL role in atherosclerosis

Answer 17

Too much circulating in blood

Become deposited into tunica intima and are oxidized by ROS

Oxidized LDL causes endothelial activation and express CAMs (ahesion receptors)

Leukocytes move into tunica intima (monocytes to macrophages) who take up oLDL and become foam cells

Question 18

Vulnerable plaques

Answer 18

Larger area of foam cells and lipid

Thin fibrous cap

Increased inflammatory cells

More likely to rupture

Question 19

Stable plaques

Answer 19

Smaller area of foam cells and lipid

Thick fibrous cap

Few inflammatory cells

Less likely to rupture

Question 20

Atherosclerotic plaque - clinical outcomes

Answer 20

Rupture, ulceration, erosion

Hemhorrage

Atheroembolism

Aneurysm formation

Question 21

Consequences of atherosclerotic disease

Answer 21

Anyuerism/rupture : plaque makes blood vessel wall weak

Occlusion by thrombus: blood forms inside plaque causing clot

Critical stenosis: over 80% occlusion

Question 22

Thrombus

Answer 22

Forms over disrupted plaque or contents of atherosclerotic plaque

Can embolism and obstruct down stream vessels

Thrombin- pre-blood clot