T3 L16: Atherogenesis Flashcards

1
Q

In which part of the vessel do atherogenic plaques develop?

A

In the tunica intima of the artery wall

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2
Q

What causes atherogenesis?

A

Migration of cells from the tunica media into the tunica intima and caused by recruitment of leukocytes and deposition of lipid from the blood

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3
Q

What are the 3 components of atherogenic plaques?

A

Cells, matrix components like collagen, and intracellular and extracellular lipids like cholesterol

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4
Q

What 2 effects does NO have on epithelium of vessels?

A

Vasorelaxation and anti-adhesive properties causing recruitment of monocytes and platelets to be inhibited

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5
Q

Which molecules transform monocytes into macrophages?

A

Cytokines like IFN-alpha, TNF-alpha, GM-CSF, and M-CSF secreted by the vascular smooth muscle cells

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6
Q

Which molecules attract monocytes to developing plaques?

A

MCP-1/CCL2, chemokines produced by endothelial cells

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7
Q

What do macrophages produce which can oxidise LDL?

A

ROS

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8
Q

What role do monocytes have in atherogenesis?

A

Transform into macrophages which can generate ROS, produce pro-inflammatory cytokines, and express scavenger receptors

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9
Q

What are remnants of LDL?

A

Smaller lipoproteins

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10
Q

What does oxidised LDL stimulate?

A

stimulates expression of VCAM-1 and MCP-1`

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11
Q

How do macrophages become foam cells?

A

When they constantly phagocytose oxidised LDL

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12
Q

What is oxidised LDL recognised by?

A

Scavenger receptors not LDL receptors

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13
Q

What are vascular smooth muscles cells responsible for?

A

Structure of the vessel wall

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14
Q

Which cells secrete PDGF and TGF-beta?

A

Endothelial cells and macrophages

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15
Q

What role do VSMC’s (Vascular smooth muscle cells) have in atherogenesis?

A

They can differentiate into macrophage-like cells and become foam cells. Activated VSMC’s can synthesise molecules like collagen which deposits in the plaque.

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16
Q

Which 2 types of cells can develop into foam cells?

A

Macrophages and vascular smooth muscle cells

17
Q

What is TGF-beta?

A

Transforming growth factor beta

18
Q

What can cause epithelial dysfunction/injury?

A

Hyperlipidaemia, hypertension, smoking, toxins, haemodynamic factors

19
Q

What is the difference between a stable and ruptured plaque?

A

Stable plaques have a thick fibrous cap, high VSMC, small amounts of lipid, and few inflammatory cells. Ruptured plaques have a thin fibrous cap, low VSMC content, large lipid content, and many inflammatory cells

20
Q

What are the 2 main theories behind atherogenesis?

A

Lipid oxidation and response to injury hypothesis

21
Q

What is familial hypercholesterolaemia?

A

A genetic disorder causing elevated levels of LDL

22
Q

What is the mechanism behind statin action?

A

They are competitive inhibitors of HMG-CoA reductase

23
Q

Lovastatin, Compactin, pravastatin, and simvastatin are types of which statin class?

A

Natural statin

24
Q

Atorvastatin and Fluvastatin are types of which statin class?

A

Synthetic statin

25
Q

What effect does blocking PCSK9 proteins have on cholesterol and why?

A

Decreased blood cholesterol. PCSK9 proteins degrade LDL receptors so blocking them allows more LDL to enter the liver and therefore leave the blood so it can’t build up in vessels