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Cardiorespiratory > Atherosclerosis and Coronary Heart Disease > Flashcards

Atherosclerosis and Coronary Heart Disease Flashcards

1
Q

non modifiable risk factors of atherosclerosis or coronary heart disease

A

age
sex
genetics

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2
Q

modifiable risk factors of atherosclerosis or coronary heart disease

A 
smoking
lipids intake
blood pressure
diabetes
obesity
sedentary lifestyle
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3
Q

Progression of atherosclerosis

A

adaptive thickening > type II lesion (macrophage foam cells) > type III (preatheroma) > type IV (atheroma: core of EC liquid) > type V (fibroatheroma: fibrous thickening) > type VI complicated lesions: thrombus, fissure, haematoma

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4
Q

Primary prevention of atherosclerosis

A

lifestyle changes

risk factor management

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5
Q

secondary prevention of atherosclerosis

A

Catheter based interventions
Revascularisation surgery
Treatment of heart failure

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6
Q

role of endothelial cells in atherosclerosis

A

barrier fx

leukocyte recruitment

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7
Q

role of platelets in atherosclerosis

A

thrombus generation

cytokine and growth factor release

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8
Q

role of monocyte/macrophage in atherosclerosis

A

foam cell formation
cytokine and growth factor release
major source of free radicals
metalloproteinases

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9
Q

role of T lymphocytes in atherosclerosis

A

macrophage activation

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10
Q

role of VSMC in atherosclerosis

A

migration + proliferation
collagen synthesis
remodelling + fibrous cap formation

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11
Q

Two main classes of macrophages

A

inflammatory (for fighting infection)

resident (homeostatic, alveolar, osteoclasts, spleen)

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12
Q

LDL

A

role of monocyte/macrophage in atherosclerosis

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13
Q

HDL

A

‘Good’ cholesterol

Carries cholesterol from ‘peripheral tissues’ including arteries back to liver (=“reverse cholesterol transport”)

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14
Q

Oxidised/modified LDL

A

Due to action of free radicals on LDL. (see later), not one single substance, families of highly inflammatory and toxic forms of LDL found in vessel walls.

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15
Q

Familial hyperlipidemia

A

Autosomal genetic disease, massively elevated cholesterol (20mmol/L). Failure to clear LDL from blood. Xanthomas and early atherosclerosis; if untreated fatal MI

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16
Q

expression of LDL receptor is _______ regulated by ________

A

negatively

intracellular cholesterol

17
Q

what are statins?

A

HMG-CoA reductase inhibitors

18
Q

In LDLR-negative patients, macrophages ________ cholesterol.

A

accumulate

19
Q

what are scavenger receptors?

A

second LDL receptor - not under feedback control - in atherosclerotic lesions that bind OxLDL

20
Q

Macrophage scavenger receptor A

A

Known as CD204
Binds to oxidised LDL
Binds to Gram-positive bacteria like Staphylococci & Streptococci
Binds to dead cells

21
Q

Macrophage scavenger receptor B

A

Known as CD36
Binds to oxidised LDL
Binds to malaria parasites
Binds to dead cells

22
Q

List oxidative enzymes macrophages have that can modify native LDL.

A

NADPH oxidase

myeloperoxidase

23
Q

What are cytokines?

A

protein immune hormones that activate endothelial cell adhesion molecules

24
Q

What are chemokines?

A

small proteins chemoattractant to monocytes

25
Q

cytokines expressed by plaque macrophages to recruit monocytes

A

IL1 which upregulates VCAM 1 (adhesion molecule)

26
Q

chemokines expressed by plaque macrophages to recruit monocytes

A

MCP1 which binds to CCR2 receptor

27
Q

“Wound healing” role of the macrophage in atherosclerosis?

A

Macrophages release complementary protein growth factors that recruit VSMC and stimulate them to proliferate and deposit extracellular matrix

28
Q

What are metalloproteinases?

A

Family of ~28 homologous enzymes.
Activate each other by proteolysis.
Degrade collagen.
Catalytic mechanism based on Zn.

29
Q

Effect of atherosclerotic plaque erosion/rupture

A

Blood coagulation at the site of rupture may lead to an occlusive thrombus and cessation of blood flow.

30
Q

Characteristics of vulnerable and stable plaques

A

Large soft eccentric lipid-rich necrotic core, increased VSMC apoptosis, reduced VSMC & collagen content, thin fibrous cap, infiltrate of activated
macrophages expressing MMPs

31
Q

Macrophage apoptosis

A

OxLDL derived metabolites are toxic eg 7-keto-cholesterol > once protective macrophage systems overwhelmed > apoptosis > release factors in central death zone > material accumulates until rupture causes it to meet blood

32
Q

What is NFkB?

A

transcription factor (nuclear factor kappa B)

33
Q

NFkB activated by?

A

Scavenger receptors
Toll-like receptors
Cytokine receptors e.g. IL-1

34
Q

NFkB activates?

A

Matrix metalloproteinases
Inducible nitric oxide synthase
Interleukin-1

Cardiorespiratory (20 decks)

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