Atherosclerosis, IHD, ACS

Question 1

Leading cause of mortality and morbidity in developed
nations; major cause of death in the developing countries

hardening of arteries

Answer 1

Atherosclerosis

Question 2

Layers of the Arterial Wall

Answer 2

intima

media

Question 3

closest to the arterial lumen

intimate with the blood

covered by single layers of endothelial cells

provides a
metabolically active barrier between circulating blood and the
vessel wall

Answer 3

Intima

Question 4

middle layer

thickest later

internal and external
laminae separate the medial from intimate and adventitia

consists of smooth muscles cells (SMCs) and extracellular
matrix and even the contractile and elastic functions of the
vessel

Answer 4

Media

Question 5

Component of medial layer that is more prominent in large arteries (i.e.
aorta and branches)

stretches during the high pressure
of systole and then recoils during diastole, propelling
blood forward

Answer 5

Elastic component

Question 6

Component of medial layer that is more prominent in smaller arteries
such as arterioles

constricts or relaxes to alter vessel
resistance and therefore luminal blood flow

Answer 6

Muscular component

Question 7

Formula for flow

Answer 7

Flow = pressure/resistance

Question 8

Performs structural, metabolic and signaling functions that
maintain homeostasis of the vessel wall

Tightly adjoined to control passage of large molecules from
the circulation

Answer 8

Endothelial cells

Question 9

Antithrombotic molecules on the surface of endothelial cells

Answer 9

heparin sulfate thrombomodulin

plasminogen activators

Question 10

Antithrombotic molecules that enter the circulation

Answer 10

prostacyclin

nitric oxide

Question 11

How do endothelial cells modulate immune response

Answer 11

resist leukocyte adhesion (oppose local inflammation)

respond to local injury or infection by expressing cell
surface adhesion molecules, which attach mononuclear cells to the endothelium, and chemokines - substances
that facilitate leukocyte recruitment to the site of injury

Question 12

Effects of inflammation to endothelial cells

Answer 12

increased permeability
increased inflammatory cytokines
increased leukocyte adhesion molecules
decreased vasodilatory molecules
decreased antithrombotic molecules

Question 13

Contractile function of vascular smooth muscle cells is modulated by

Answer 13

vasoactive substances:
- circulating molecules (e.g. angiotensin II)
- those released from local nerve terminals (e.g.
Acetylcholine)
- others originating from the overlying endothelium (e.g.
endothelin and NO)

Question 14

Synthetic function of vascular smooth muscle cells is modulated by

Answer 14

collagen, elastin and proteoglycans that form the bulk of
the vascular extracellular matrix

vasoactive and inflammatory mediators, including
interleukin-6 (IL-6) and tumor necrosis factor (TNF)

Question 15

Made up by fibrillar collagen, elastin and proteoglycans in the
medial layer, which maintain structural integrity of the vessel

Native fibrillary collagen can inhibit SMC proliferation in vitro

Influences cellular response to stimuli
- matrix-bound cells respond in a specific manner to
growth factors and resist apoptosis

Answer 15

Extracellular matrix

Question 16

The earliest visible lesion of atherosclerosis

Yellow discoloration on the artery’s inner surface

Neither protrude substantially into the arterial lumen nor
impede blood flow

Exist in the aorta and coronary arteries of most people by age
20

Do not cause symptoms

In some locations in the vasculature, they regress over time

Answer 16

Fatty streak

Question 17

Formation of fatty streak

Answer 17

1. endothelial dysfunction
2. lipoprotein entry and modification
3. leukocyte recruitment
4. foam cell formation

Question 18

Primary event in atherogenesis

Results from exposure to divers

Answer 18

Endothelial dysfunction

Question 19

an endogenous vasodilator, an
inhibitor of platelet aggregation, and an anti-inflammatory
substance

Answer 19

nitric oxide

Question 20

arteries with few branches vs bifurcated vessels

Answer 20

arteries with few branches - relative resistance to atherosclerosis

bifurcated
vessels (e.g., common carotid and left coronary a.)
contain common sites for atheroma formation

Question 21

Effect of toxic chemical environment on blood vessels

Answer 21

these stimuli increase endothelial production of reactive
oxygen species (superoxide anion)

with this, the cells promote local inflammation

Question 22

Activated state (by stressors) of endothelium is manifested by

Answer 22

impairment of permeability barrier,

release of inflammatory
cytokines

increased production of cell surface adhesion
molecules that recruit leukocytes, altered release of
vasoactive substances (e.g. prostacyclin and NO)

interference with normal antithrombotic properties

Question 23

Effect of increased endothelial permeability

Answer 23

allows the entry of LDL

into the intima

Question 24

How does LDL accumulate in the subendothelial space

Answer 24

by binding to

proteoglycans in the ECM

Question 25

How does hypertension further promote retention of lipoproteins in the intima

Answer 25

by accentuating the production of LDL-binding proteoglycans by SMC

Question 26

In relation to LDL, what could happen in diabetic patients with sustained hyperglycemia?

Answer 26

glycation of LDL can occur- a modification that may ultimately render LDL antigenic and proinflammatory

Question 27

In the fatty streak, and likely throughout plaque development,, what does modified LDL do?

Answer 27

promotes leukocyte recruitment and | foam cell formation

Question 28

cells involved in leukocyte recruitment

Answer 28

monocytes | T lymphocytes

Question 29

Process of foam cell formation

Answer 29

Monocytes adhere to and penetrate the intima  differentiate into macrophages and imbibe lipoproteins to form foam cells  Family of "scavenger" receptors bind and internalize mLDL  evade negative feedback inhibition and permit engorgement of the macrophages with cholesterol and cholesteryl ester  typical appearance of foam cells

Question 30

 Impaired efflux of foam cells as compared to the rate of | influx, as well as local proliferation, leads to

Answer 30

accumulation in the plaque

Question 31

Effect of inefficient clearance of foam cells

Answer 31

accumulation of cellular debris and extracellular lipids  forming the lipid-rich center of a plaque necrotic core

Question 32

How does the structure of the fibrous cap contribute to the plaque integrity?

Answer 32

Lesions with thick fibrous caps may cause pronounced arterial narrowing, they have less propensity to rupture.  Conversely, plaques that have thinner caps (and often appear less obstructive by angiography) tend to be fragile and more likely to rupture and incite thrombosis

Question 33

Stages of plaque development

Answer 33

Fatty streak - plaque progression - plaque disruption

Question 34

Stable vs Vulnerable Plaques

Answer 34

Stable Plaque o small lipid core and a thick fibrous cap Vulnerable plaque o large lipid core and a relatively thin fibrous cap o subject to rupture, resulting in thrombosis --> myocardial infarction