Cv Path Atherosclerosis

Front 1

Describe the first stage of atherosclerosis

Back 1

-Asymptomatic
-Takes years to develo
-Involves build up of atherosclerotic plaques in the arteriole wall
-Plaque made from fat cells and extracellular material
-Worst it can cause is exertional angina
-As plaque builds up there is outward remodeling to preserve the lumen
-Body can make new collateral vessels via neovasculatization

Front 2

Describe the second stage of atherosclerosis

Back 2

-Acute thrombus formation in the lumen
-Starve distal tissue of oxygen and nutrients leading to tissue death and dysfunction
-This can lead to unstable angina

Front 3

Which lipoproteins trigger atherosclerosis?

Back 3

-The ones that have apo-B,
-LDL and chylomicron remnants are the most atherogenic

Front 4

What is a good biomarker for overall risk of atherosclerosis?

Back 4

LDL

Front 5

Describe the stages of atherosclerosis that occurs in the preteen years

Back 5

-If lipoproteins stay in the vasculatrure for long enough they can get stuck in the subendothelial space in certain areas of the arterial tree.
-In places with flow disturbances (such as branching points) there are proteoglycans to cushion the flow
-Later in life the apoB lipoproteins stick to these proteoglycans
-In the preteen years you start to retain LPs

Front 6

Back 6

Unoccluded coronary artery

Front 7

Back 7

Occluded coronary artery

Front 8

Back 8

Subendothelial lipoprotein aggregation and matrix retention

Front 9

Describe the phase of atherosclerosis that occurs in a persons teenage years

Back 9

-Retained LPs undergo modification, such as oxydation
-They start to look like bacteria
-Antibodies start to recognize the LPs
-Macrophages are called in

Front 10

Describe the phase of atherosclerosis that occurs when a person reaches their 20s

Back 10

-Monocytes come in and eat the retained lipoproteins
-They try to metabolize the fats
-The cholesterol becomes stored inside the macrophages and they develop a foamy appearance
-Bioactive components trigger the macrophages

Front 11

Describe the phase of atherosclerosis that occurs in a persons 20s and beyond

Back 11

-Part of the maladaptive response involves continual recruitment of inflammatory cells
-There is no clean up phase
-There is continuous recruitment of inflammatory cells
-Dead cells that are not cleaned up leads to necrosis
-This can lead to breakage/eruption of the plaque which exposes thrombogenic material

Front 12

What causitive evidence is there to support the response to retention model of atherosclerosis

Back 12

-When there are no ApoB lipoprotiens there is no maladaptive inflammatory response and no atherosclerosis
-When there is decreased retention there is decreased atherosclerosis
-LP retention occurs before the earliest phase of atherogenesis

Front 13

What is the root cause of atherosclerosis?

Back 13

ApoB

Front 14

Describe the reversibility of plaque formation leading to atherosclerosis

Back 14

As the inflammatory response gets going, new proteoglycans get made that are stickier than the first ones and other molecules are made that further aid retention. Retention becomes amplified as the lesion gets going. There is reversibility but regression is a lot harder towards the end compared to the beginning.

Front 15

Describe the lesions that are most susceptible to rupture

Back 15

-Not neccessarilly the biggest
-Most susceptible are the ones with the most necrosis and the thinnest scar
-Normally the scar is protective, but if it thins out then the plaque is more likely to rupture

Front 16

Describe the necrotic core

Back 16

-"Graveyard for dead macrophages"
-These are the macrophages that come in as part of the inflammatory response
-They die but don't get eaten
-They become necrotic
-This necrotic core triggers inflammation, provides material that can trigger thrombosis, is filled with proteases and can put a stress on the fibrous cap.

Front 17

What causes the necrotic core to form?

Back 17

Failure to clear the dead macrophages

Front 18

Describe the relationship between smooth muscle cells and scar formation

Back 18

-There are smooth muscle cells that make the scar.
-When those smooth muscle cells start to die the scar formation tones down.
-As the scar gets eaten away by some of the proteases in the necrotic core the smooth muscle cells are not robust enough to make new scar.

Front 19

Back 19

-Fatty streak
-Focal accumulation of cholesterol

Front 20

Back 20

-Foam cells
-Cellular component of the fatty streak
-Macrophages have eaten the lipids and are in the subendothelial space

Front 21

Back 21

Plaque rupture

Front 22

Describe the treatment of atherosclerosis

Back 22

-The only successful treatment is getting rid of the root cause
-Statins lower LDL and decrease cardiac disease

Front 23

What two things are needed for atherosclerosis?

Back 23

-"High" levels of apoB-lipoproteins in the bloodstream
-A "susceptible" arterial wall (i.e., susceptible to apoB-LP retention or responses to retention)

Front 24

What are some risk factors for arterial wall susceptibility?

Back 24

-Family history
-Low HDL
-Smoking
-Diabetes
-Age
-?CRP

Future: Gene chips

Front 25

What therapeutic approach should be used to prevent and reverse atherosclerosis?

Back 25

Decrease the probability of ApoB-LP entry and then retention in the subendothelium

Front 26

Why might a patient who smokes and has high LDL not get atherosclerosis?

Back 26

Genes are incredibly important

Front 27

Describe the treatment for atherosclerosis

Back 27

Therapeutic Lifestyle Change (TLC):
Improve Diet
Weight Reduction
Physical Activity

Pharmacologic Treatment:
Statins (HMG-CoA reductase inhibitors)
Fibrates
Niacin
Bile acid sequestrants
Cholesterol absorption inhibitors

Front 28

Describe the phrase "earlier is better"

Back 28

-Atherosclerosis begins at an early age
-The early stages are more easily reversible
-The less ApoB you have the better