Atherosclerosis (Quiz 2) Flashcards
(146 cards)
1
Q
What was the incorrect description of atherosclerosis?
A
Fat builds up on the surface of passive artery walls. If a deposit (plaque) grows large enough, it eventually closes off an affected pipe, preventing blood from reaching its intended tissue. Blood-starved tissue dies, and heart attack or stroke occurs.
2
Q
What is another term for plaque?
A
A deposit
3
Q
How long ago did investigations about atherosclerosis begin?
A
More than 20 years ago
4
Q
What do arteries bear little resemblance to?
A
Inanimate pipes
5
Q
What do arteries contain?
A
Living cells that communicate constantly with one another and their environment
6
Q
What do the cells in arteries participate in?
A
Development and growth of atherosclerotic deposits, which arise in, not on, vessel walls
7
Q
Where do atherosclerotic deposits arise?
A
In (not on) vessel walls of arteries
8
Q
How many deposits expand so much that they shrink the bloodstream to a pinpoint?
A
Relatively few
9
Q
What do most heart attacks and many strokes stem from?
A
From less obtrusive plaques that rupture suddenly, triggering the emergence of a blood clot, or thrombus, that blocks blood flow
10
Q
What is another name for a blood clot?
A
A thrombus
11
Q
What does inflammation underlie in atherosclerosis?
A
All phases of the disorder, from the creation of plaques to their growth and rupture
12
Q
What does inflammation literally mean?
A
“on fire”
13
Q
What does this revised conception of atherosclerosis suggest and resolve?
A
Suggests new ideas for detecting and treating atherosclerosis. Resolves why many heart attacks strike without warning and why certain therapies meant to avert heart attacks frequently fail.
14
Q
What does society need advances in?
A
Prevention, detection, and therapy of athersclerosis
15
Q
How do heart attack and stroke compare to cancer as a cause of death in industrial nations and developing countries?
A
They exceed cancer as a cause of death in industrial nations and are growing more prevalent in developing countries.
16
Q
What fuels the development and progression of atherosclerosis?
A
Inflammation
17
Q
What is atherosclerosis?
A
The dangerous accumulation of fat-laden deposits, or plaques, in the arteries
18
Q
What can inflammation cause?
A
Certain plaques to rupture.
19
Q
What do blood clots tend to do (plaques, arteries)?
A
Tend to form over ruptured plaques and can then occlude arteries, leading to atherosclerotic complications like heart attack and stroke
20
Q
What does LDL stand for?
A
Low-density lipoprotein or “bad cholesterol”
21
Q
What does excess LDL (low-density lipoprotein) trigger?
A
Arterial inflammation
22
Q
What reduces arterial inflammation?
A
Cholesterol-lowering therapies
23
Q
What happens after sensing that a microbial attack has begun?
A
Certain white blood cells convene in the apparently threatened tissue
24
Q
What are white blood cells?
A
The immune system’s frontline warriors
25
When do white blood cells convene in a tissue?
When it senses that a microbial attack has begun
26
What do white blood cells do in a threatened tissue?
Secrete an array of chemicals intended to limit any infection
27
What chemicals do white blood cells release in a threatened tissue?
Oxidants (able to damage invaders) and signaling molecules (orchestrate the activities of defensive cells; ex: small proteins called cytokines)
28
What are oxidants?
Chemicals that are able to damage invaders
29
What are signaling molecules?
Molecules that orchestrate the activities of defensive cells. Ex: small proteins called cytokines
30
How do researchers document an inflammatory response?
By identifying inflammatory cells or mediators of their activities in a tissue
31
What are LDL particles composed of?
Fatty molecules (lipids) and protein
32
What do LDL particles do?
Transport cholesterol (another lipid) from their source in the liver and intestines to other organs
33
What is cholesterol?
A type of lipid that comes from the liver and intestines
34
What do excessive amounts of LDL and cholesterol promote?
Atherosclerosis
35
What have researchers been studying to learn more about LDL?
Cultured cells and animals
36
What can LDLs pass in and out of at reasonable concentrations in the blood?
The intima
37
What does the intima consist of?
Consists mainly of the endothelial cells that line vessel walls, the underlying extracellular matrix (connective tissue), and smooth muscle cells (matrix producers)
38
What happens to LDL when it is in excess?
Tends to become stuck in the matrix
39
When does the trouble begin for atherosclerosis?
When LDLs from the blood collect in the intima/matrix
40
What is the intima?
The part of the arterial wall closest to the bloodstream
41
What are the bad and good cholesterols?
Low-density lipoprotein (LDL) and high-density lipoprotein (HDL)
42
What do lipoproteins do?
Transport cholesterol in the bloodstream
43
What do various tissues use cholesterol for from the LDLs?
To repair membranes or produce steroids
44
What do HDLs do?
Transport cholesterol to the liver for excretion or recyling
45
What happens to LDL when it accumulates within vessel walls?
Its components become oxidized and altered in other ways; these components then incite an inflammatory response that progressively alters arteries
46
What are the protective effects of HDL?
Removes cholesterol from arteries, combats atherosclerosis by interfering with LDL oxidation
47
What happens to the lipids as LDLs accumulate?
They undergo oxidation and their proteins undergo both oxidation and glycation (binding by sugars)
48
What is glycation?
Binding by sugars
49
What happens when LDL lipids/proteins undergo oxidation and glycation (2)?
Cells in the vessel wall interpret the change as a danger sign and call for reinforcements from the body’s defense system—i.e., adhesion molecules on endothelial cells (facing the blood) latch onto inflammatory cells called monocytes, causing cells to drop from circulation and attach to the artery wall; also spurs the endothelial cells and smooth muscle cells of the intima to secrete chemicals called chemokines, which attract monocytes
50
What are monocytes and where are they normally?
Inflammatory cells that normally circulate in the blood
51
What are chemokines and what do they do?
Chemicals secreted from endothelial cells and smooth muscle cells that attract monocytes; induce monocytes to multiply and mature into active macrophages
52
When adhesion molecules on epithelial cells latch onto monocytes, what do the monocytes do?
They squeeze between endothelial cells and follow the chemical trail to the intima (chemokines secreted from endothelial cells and smooth muscle cells attract monocytes in intima)
53
What do endothelial cells and smooth muscle cells of the intima do when LDL lipids/proteins undergo oxidation and glycation?
Secrete chemokines
54
Where are adhesion molecules and what do they do?
On the blood-facing surface of endothelial cells, they latch onto monocytes, causing the cells to drop from circulation and roll along and attach to the artery wall.
55
What induces monocytes to multiply and mature into active macrophages?
Chemokines and other substances by the endothelial and smooth muscle cells
56
What are macrophages?
Fully armed warriors that clear perceived invaders from the vessel wall
57
What do macrophages react to?
Proteins emitted by stimulated endothelial and intimal smooth muscle cells (like chemokines?)
58
What do macrophages have on their surface?
Molecules called scavenger receptors which capture modified LDL particles and help macrophages ingest them.
59
What are scavenger receptors and where are they located?
Receptors that capture modified LDL particles and help macrophages ingest them; located on the surface of macrophages
60
What happens to macrophages as they ingest modified LDL particles?
They become so packed with fatty droplets that they look foamy—called foam cells.
61
What are foam cells?
Fat-filled macrophages
62
What follows adhesion molecules and chemokines into the intima?
Monocytes and T lymphocytes
63
What are T lymphocytes?
White blood cells that represent a different branch of the immune system and release cytokines (chemicals that secrete monocytes) that amplify inflammatory activities in artery walls
64
What is the fatty streak?
The foamy macrophages and a lesser number of T lymphocytes; a precursor of the complex plaques that later disfigure arteries; earliest form of atherosclerotic plaque
65
How early do Americans harbor nascent plaques?
Teens
66
When does inflammation occur?
When certain white blood cells invade and become active in a tissue
67
What do modified LDLs (from chemical alterations) stimulate?
Endothelial cells to display adhesion molecules which latch onto monocytes and T cells in the blood
68
What do endothelial cells secrete?
Chemokines, which lure the snared cells into the intima
69
Where do the monocytes mature?
In the intima, into active macrophages
70
What do the macrophages and T cells produce?
Many inflammatory mediators, including cytokines (carry signals between immune system cells) and factors that promote cell division
71
How does a fibrous cap form over the lipid core?
Molecules induce smooth muscle cells of the media to migrate to the top of the intima, multiply and produce a tough, fibrous matrix that glues the cells together
72
What does the cap do?
Adds to the size of the plaque but also walls it off safely from blood
73
What can weaken the cap?
Inflammatory substances secreted by foam cells that digest matrix molecules and damage smooth muscle cells, which then fail to repair the cap
74
What is tissue factor and where is it displayed?
A potent clot promoter in foam cells (fat-filled macrophages)
75
What may foam cells display?
Tissue factor, a potent clot promoter
76
What happens if the weakened plaque ruptures?
Tissue factor will interact with clot-promoting elements in the blood, causing a thrombus, or clot, to form. If the clot is big enough, it will halt the flow of blood to the heart (heart attack).
77
What is a thrombus?
A blood clot
78
What is a heart attack?
Death of cardiac tissue
79
What can happen to clots/thrombus if they dissolve before they cause a heart attack or stroke?
They can stimulate plaque expansion
80
What facilitates healing in an inflammatory response?
Macrophages that release molecules to facilitate healing
81
What is the healing process of inflammation in atherosclerosis?
Remodels artery walls, eventually generating a bigger, more complicated plaque (doesn’t restore walls to their original state)
82
What do macrophages, endothelial cells, and smooth muscle cells of the inflamed intima help?
They secrete factors that prod smooth muscle cells of the media to migrate to the top of the intima, replicated and synthesize components of the extracellular matrix
83
What is the media?
The tissue under the intima
84
What 3 things secrete factors that prod smooth muscle cells of the media to migrate to the top, replicate, and synthesize components of the extracellular matrix?
Macrophages, endothelial cells, and smooth muscle cells
85
What do the cells and matrix molecules make in the healing process?
They coalesce into a fibrous covering overlying the original atherosclerotic zone
86
What happens as the cap matures?
The zone underneath generally changes somewhat—some fraction of the foam cells die, releasing lipids. Thus this region under the cap is called the lipid or necrotic core
87
What is the region under the cap called?
The lipid or necrotic core
88
How do atherosclerotic plaques take up space, and what is the significance of this?
Expand outward, rather than impinging on an artery’s blood-carrying channel. This preserves blood flow for quite some time.
89
What happens when plaques push inward?
They restrict the blood channel—condition called stenosis
90
What is stenosis and what does it do?
A condition in which plaques push inward and restrict the blood channel; impedes blood delivery to tissues, especially at moments of greater need when the arteries would usually expand
91
What is angina pectoris?
A feeling of tightness, squeezing, or pressure usually under the breastbone
92
What are intermittent claudication?
Symptoms of painful cramping of the calves or buttocks during exertion; caused by narrowing in other arteries
93
How much percent of heart attacks are caused by a plague growing so large that it halts blood flow in an artery?
Only 15%
94
When do most heart attacks occur?
After a plaque’s fibrous cap breaks open, prompting a blood clot to develop over the break.
95
What are the characteristics of plaques most likely to fracture?
They possess a thinned cap, a large lipid pool, and many macrophages. Vulnerability stems from inflammation
96
What does the integrity of the fibrous covering depend on?
Steel-strong collagen fibers made by smooth muscle cells
97
When do mediators of the process compromise the cap?
When something causes inflammation to flare in a relatively quiet plaque
98
What are the two ways in which mediators can compromise the cap?
Inflammatory mediators can 1. stimulate macrophages to secrete enzymes that degrade collagen or 2. inhibit smooth muscle cells from extruding the fresh collagen required to repair and maintain the cap
99
When do clots form?
When blood seeps through a fissure in the cap and encounters a lipid core teeming with proteins able to facilitate blood coagulation
100
What is an example of clots forming?
Molecules on T cells in the plaques spur foam cells to manufacture high levels of tissue factor, a potent clot inducer. Circulating blood contains precursors of the proteins involved in cascade of reactions responsible for clot formation. When blood meets tissue factor and other coagulation promoters in a plaque’s core, the clotting precursors jump into action.
101
What do bodies do to fight against clots?
Produce substances that can prevent a clot from materializing or can degrade it before it causes a heart attack or stroke. Can also take drugs to clear clots.
102
What do clots in plaques do to fight against bodies?
Inflamed plaques release chemicals that impede the innate clot-busting machinery.
103
What happens if a clot is cleared naturally or with the aid of drugs?
Healing process may kick in, restoring the cap but also further enlarging the plaque by forming scar tissue.
104
What are the two ways plaques grow in fits and starts?
As triggers of inflammation come and go and as clots emerge and dissolve but leave scars
105
Why do many heart attacks seem to come from out of the blue?
The plaques that rupture do not necessarily protrude very far into the blood channel and so may not cause angina or appear prominently on images of the channel.
106
Which types of therapies frequently fail to prevent future heart attacks?
Therapies that focus on widening the blood passage in semioccluded arteries (balloon angioplasty or insertion of wire-cage stents) or on surgically creating a bypass —> ease angina, not necessarily heart attacks (plaques that cause less narrowing but are more prone to rupturing may be at more risk)
107
What happens when stenosis is the problem, and why?
Treated arteries often become reoccluded fairly rapidly, in part because treatments can trigger a robust inflammatory response
108
What do many risk factors for atherosclerosis exhibit?
Inflammatory properties
109
How many of all patients who have angina or have had a heart attack do not have above-average LDL levels? What argues against this statistic?
Half of all patients. Typical LDL levels in Western society exceed by far the body’s needs and can actually promote arterial disease
110
What did the National Institutes of Health now label LDL-cholesterol levels as optimal?
Below 100 mg per dL (deciliter) of blood
111
What did the National Institutes of Health now suggest for when to start drug treatment for certain people with multiple risk factors?
At 130 mg/dL instead of 160
112
What are the guidelines for initiating lifestyle changes (diet and exercise) and for considering drug treatment for adults with a relatively low risk of heart disease?
Lifestyle changes at 160 mg/dL and drug treatment at 190 mg/dL
113
What risk factors may enhance inflammatory properties of LDL?
Diabetes, smoking, obesity, giotensin II (hormone responsible for hypertension or high blood pressure)
114
What does diabetes do to enhance inflammatory properties of LDL?
Elevate glucose levels in the blood —> enhance the glycation and thus inflammatory properties
115
What does smoking do to foster arterial inflammation even in individuals with average LDL levels?
Causes oxidants to form and might hasten the oxidation of LDL’s constituents, thereby fostering arterial inflammation
116
How does high blood pressure affect inflammation in LDL?
Not directly, but a hormone responsible for hypertension (giotensin II) appears to incite inflammation. May give rise to hypertension and atherosclerosis simultaneously
117
What happens as levels of HDL decline?
Likelihood of suffering a heart attack goes up
118
What do many physicians measure in the blood?
Levels of LDL, level of HDL, and ratio of LDL (or LDL plus its various relatives) to HDL
119
How may HDL achieve its beneficial effects?
In part by reducing inflammation. It transports cholesterol and antioxidant enzymes able to break down oxidized lipids.
120
Do arterial infections contribute to inflammation in the arteries since inflammation usually blocks and eliminates infectious agents?
Recent work suggests atherosclerosis can develop in the absence of infection. However, there is still evidence that certain microorganisms such as herpesviruses or the bacterium Chlamydia pneumonia (frequent cause of respiratory infections) could induce or aggravate atherosclerosis
121
What is Chlamydia pneumonia’s link to atherosclerosis?
As a frequent cause of respiratory infections, it appears in many atherosclerotic plaques and its constituents can evoke inflammatory responses by macrophages and by vascular endothelial and smooth muscle cells
122
What is an echo effect?
When infections might act from a distance
123
How does an echo effect work?
Inflammatory mediators escape into the blood and travel to distant sites—> stimulate white cells in atherosclerotic plaques, prompting plaque growth or rupture.
124
Do antibiotics prevent recurrent heart attacks?
Recent trial suggests antibiotics do not forestall recurrences in heart attack survivors.
125
What types of medicines may slow atherosclerosis?
Anti-inflammatory medicines like aspirin
126
What class of drugs does aspirin belong to?
NSAIDs (nonsteroidal anti-inflammatory drugs)
127
What are NSAIDs?
nonsteroidal anti-inflammatory drugs that include aspirin, ibuprofen, naproxen, etc.
128
What does aspirin do?
Blocks formation of certain lipid mediators of inflammation, including the prostaglandins which generate pain and fever. May also shield against heart attacks and mini strokes (technically, transient ischemic attacks or TIAs)
129
What is the downside of aspirin?
The low doses that give protection probably reduce the clotting propensity of blood instead of quieting inflammation
130
What may selective inhibitors of the prostaglandin-producing enzyme COX-2 do?
May enhance thrombus development in some patients (blood clot)
131
What may enhance thrombus development in some patients?
Selective inhibitors of the prostaglandin-producing enzyme COX-2
132
What do we think about cortisone and related steroids?
Could prove too toxic for long-term use; no data supports their utility in reducing atherosclerotic complications
133
What could happen even if anti-inflammatory drugs proved effective?
Might have to be given for years on end to keep atherosclerosis at bay —> ongoing interference with inflammation could come with increased risk of infection
134
What are some of the author’s hopes for the future?
Devise a way to halt inflammation of atherosclerosis without undermining overall immunity or defusing the triggers at the root of arterial inflammation.
135
What can reduce the risk of a heart attack?
Heart-healthy diet, regular exercise, weight loss for obese individuals (also combats diabetes)
136
What do lipid-lowering drugs do?
Reduce likelihood of atherosclerotic complications and can prolong life among individuals with a broad range of risk levels. However, they do not seem to reduce arterial stenosis substantially. May limit inflammation, thereby minimizing plaque build-up and less rupturing of existing plaques
137
What are statins?
Widely prescribed lipid-controlling drugs that decrease levels of LDL and related bad lipids by increasing their disposal in the body
138
What may statins be able to do?
Decrease inflammation in patients. Isolated cells and lab animals indicate that the drugs’ anti-inflammatory effects may not depend entirely on changing the concentrations of lipids in the blood. May limit availability of chemicals that enable cells to respond to inflammatory mediators
139
May experimental drugs that aim at other risk factors for heart disease and stroke help with anti-inflammatory effects? What are some examples of agents?
Yes—agents that raise levels of HDL or limit the action of angiotensin II
140
Have treatment with antioxidant vitamins been promising?
No, quite disappointing
141
What do doctors need to detect better?
Dangerous atherosclerosis in people whose lipid levels look too good to justify treatment
142
What is a new kind of test that may prove effective in detecting people at risk?
Blood tests combining lipid testing with monitoring of a substance called C-reactive protein
143
What does the presence of C-reactive protein in the blood signify?
That inflammation is occurring somewhere in the body; highly elevated levels, even with low LDL values, indicate increased risk of heart attack or stroke. In at least one study, delivery of statins to people with below-average LDL concentrations but high C-reactive protein levels reduced incidence of heart attack relative to rate in matched group of patients who received no treatment
144
Do some physicians already incorporate tests of C-reactive protein in their practices?
Yes
145
What may noninvasive methods do?
Noninvasive methods for specifically identifying vulnerable plaques may help pinpoint individuals who lack strong warning signs of risk—ideas include measuring heat of blood vessels (heat accompanies inflammation) and altering existing imaging technologies like MRI or CT scans to improve ability to visualize material inside vessel walls. Geneticists hunt for gene variants that make people more vulnerable to chronic inflammation and to atherosclerosis.
146
Describe the study that looked at C-reactive protein.
From Paul Ridker of Brigham and Women’s Hospital: cholesterol levels and C-reactive protein levels combined is a more accurate way to measure. Grouped cholesterol levels and C-reactive protein levels into 5 quintiles and determined relative risk in people (danger level of 1 to those who fell in lowest quintile and calculated how much that risk multipled in others). Found that even in low cholesterol values, high C-reactive protein values signify elevated risk for heart attack or stroke.
