Lesson 2: Cad: Atherosclerosis And Arterioscerosis

Front 1

What is the LEADING cause of death in the United States?

Back 1

Cardiovascular disease

Front 2

What are the top 3 causes of death in the United States?

Back 2

Cardiovascular disease, cancer, and accidents.

Front 3

Coronary artery disease (CAD)

Back 3

Involves atherosclerosis in the coronary arteries

Front 4

Atherosclerosis

Back 4

Progressive narrowing of the arteries due to plaque formation

Front 5

Arteriosclerosis

Back 5

Hardening of the arteries.

Front 6

Ischemia

Back 6

A deficiency of blood flow to the heart caused by CAD

Front 7

Myocardial Infarction

Back 7

A heart attack due to ischemia leading to irreversible damage and necrosis.

Front 8

Prevalence of Cardiovascular Disease

Back 8

> 1.6 million heart attacks

~500,000 deaths due to heart attacks

~1 in 5 deaths was attributable to cardiovascular diseases

1 in 2.7 deaths was attributable to cardiovascular diseases.

Front 9

What is the leading cause of death from cardiovascular disease?

Back 9

Coronary artery disease.

Front 10

What are the top 3 risk factors for CAD?

Back 10

Diabetes, low HDL-cholesterol, and hypertension.

Front 11

Monocyte

Back 11

A type of WBC and is part of immune system. Produced by bone marrow from hematopoietic stem cells (from monoblasts). 50% stored in spleen, 50% circulate in blood. Monocytes triggered to damaged site or inflammation. Monocyte enters damaged tissue through endothelium of blood vessel,and undergoes series of changes to become macrophage.

Front 12

Macrophage

Back 12

Predominant cells involved in creating the progressive plaque lesions of atherosclerosis. Monocyte enters endothelium of blood vessel for become a macrophage.

Front 13

Stem cell + LY6C receptor=

Back 13

LY6C+ monocyte

Front 14

Chylomicrons

Back 14

Exogenous transport from intestines to liver.

Front 15

HDL

Back 15

Reverse cholesterol transport.

Front 16

VLDL

Back 16

Transport triacylglycerols to cells.

Front 17

LDL

Back 17

Delivers cholesterol to arterial tissue.

Front 18

What are 2 things macrophages will do?

Back 18

Take up lipids to become foam cells or send out/release cytokines.

Front 19

What is happening until a signal from inflamed tissue is received?

Back 19

The MCP-1 receptor attached to the Ly6C+ inflammatory monocyte circulate until a signal from inflamed tissue is received.

Front 20

Macrophages and foam cells secrete growth factors which lead to what?

Back 20

Cell proliferation (cell growth) and matrix production of plaque, as well as metalloproteinases, which lead to matrix degeneration (breakdown of endothelial cells in intima)

Front 21

MCP-1 is released in response to what?

Back 21

Pathogen (LDL)

Front 22

The monocyte enters the intima via what mechanisms and what adhesion molecules?

Back 22

Rolling: E-selectin

Sticking: VCAM & ICAM

Transmigration: MCP-1 (from endothelium to intima

Front 23

What modifications does the LDL undergo?

Back 23

Oxidation of both the lipids and the apo B

Front 24

Monocytes enter into what of the artery wall?

Back 24

Intima.

Front 25

Once inside the intima the monocytes differentiate into a ______?

Back 25

Macrophage.

Front 26

Macrophages release _____ and take up lipids to form _________.

Back 26

cytokines

foam cells

Front 27

Once inside the artery wall LDL is modified in what two ways?

Back 27

Oxidation of lipids and apo-B.

Front 28

Modified LDL activates _____ that is responsible for attracting _______ into the artery wall?

Back 28

MCP-1

Monocytes

Front 29

The adhesion molecule _____ is responsible for rolling the monocyte while VCAM-1 and ICAM-1 are responsible for ______ which then leads the monocyte to do what?

Back 29

rolling

sticking

transmigrate

Front 30

Types of cytokines?

Back 30

TNF and IL-1. They activate endothelial cells to express adhesion molecules that bind monocytes, making them available for recruitment into the subendothelial space by MCP-1.

Front 31

How do macrophages take up LDL?

Back 31

Through scavenger receptors, some recognize the different forms of modified LDL, accumulate the lipid, and are converted into lipid-rich foam cells which are the hallmark of atherosclerosis.

Front 32

Atheroma

Back 32

Accumulation and swelling in artery walls that is made up of (mostly) macrophage cells that contain lipids (fat).

Front 33

Macrophages also produce growth factors that lead to what?

Back 33

Cell proliferation and matrix production, and metalloproteinases that lead to matrix degeneration.

Front 34

Stage I atherosclerosis

Back 34

monocyte adhesion/migration

Front 35

stage II atherosclerosis

Back 35

foam cells (lipid containing macrophages) in intima.

Front 36

stage III atherosclerosis

Back 36

appearance of extracellular lipid.

Front 37

stage IV atherosclerosis

Back 37

core formation. protective mechanism. extracellular lipid coalescing into the center of the plaque.

Front 38

Stage V atherosclerosis

Back 38

fibrous cap and core formation. fully formed lipid core and well developed cap of fibrous tissue separating the core from the lumen.

Front 39

Stage IV atherosclerosis

Back 39

thrombosis.

Front 40

unstable angina with plaque disruption

Back 40

the fibrous cap is torn, projects into the lumen, exposing a mass of thrombus filling the lipid core.

Front 41

Plaque accumulation in the intima signals what?

Back 41

Signals smooth muscle cells to multiply and move from the tunica media causing the smooth muscle cells to multiply and move from the tunica media of the coronary arteries to the surface of the plaque near the endothelial layer of the intima.

Front 42

CD40 Ligand

Back 42

Signal triggering molecule. On activated platelets, triggers and inflammatory reaction of the macrophage.

Front 43

What does the macrophage do in response to CD40 and cytokines?

Back 43

macrophage releases proteolytic enzymes that degrade collagen and other structurally important molecules of the plaque's fibrous cap.

Front 44

What % of surface area must a thrombus occupy of the lumen in order to cause symptoms?

Back 44

75%

Front 45

90% obstruction of the lumen causes what?

Back 45

anoxia, the complete deprivation of oxygen, and infarction, a mode of cell death.

Front 46

The majority of coronary events occur where there is less than __% stenosis.

Back 46

70%

Front 47

Thrombus formation

Back 47

Crucial factor in the precipitation of unstable angina or myocardial infarction, as well as occlusion during or following angioplasty.

Front 48

What is the best-known function of HDL?

Back 48

The efflux of cholesterol from modified LDL. This prevents macrophages from being converted into foam cells.

Front 49

Paraoxonase

Back 49

Transported in plasma as a component of HDL to the intima. Known to inhibit the oxidative modification of LDL which prevents the formation of modified LDL

Front 50

CETP

Back 50

Cholesteryl ester transfer protein. Located in the blood, transfers oxidized lipids from LDL to HDL.

Front 51

HDL inhibits ______ which prevents adhesion molecule expression.

Back 51

Sphingosine Kinase.

Front 52

How does HDL affect cardiovascular health?

Back 52

Increases efflux of cholesterol from foam cells

Inhibits the oxidation of LDL due to paraoxonase

Collects oxidized lipids from LDL due to cholesteryl ester transfer protein (CETP) transferring oxidized lipids from LDL to HDL

Inhibits endothelial cell sphingosine kinase which prevents adhesion molecule expression

Front 53

CRP

Back 53

C-reactive protein. Found in blood, rise in response to inflammation. Synthesized by liver in response to factors released by fat cells adipocytes.

Front 54

Healthy CRP values for men?

Back 54

.3-8.6mg/L

Front 55

Healthy CRP values for women?

Back 55

.2-9.1 in women not on hormone replacement therapy.

Front 56

Risk levels for cardiovascular disease CRP values?

Back 56

low= less than 1mg/L
average=1-3mg/L
high=greater than 3mg/L

Front 57

CRP is a greater marker for risk of cardiovascular event than LDL itself?

Back 57

YES!

Front 58

What are 4 things that increase C-reactive proteins?

Back 58

smoking, chronic inflammation, obesity, and estrogen.

Front 59

what are 3 things that decrease C-reactive proteins?

Back 59

Aspirin, statin, thiazolidinediones.

Front 60

Does aspirin reduce CRP?

Back 60

Studies can be mixed, but it shows "no".

Front 61

Does weight loss reduce CRP?

Back 61

In a study, reduced by 26%.

Front 62

What helps lower high C-reactive protein levels?

Back 62

Weight loss if overweight, regular aerobic exercise, statin therapy (medication that lowers cholesterol)