Hello and welcome to Demystifying Medicine!
In this video,
we will be talking about atherosclerosis and exploring how the
immune system has a part to play in this disease.
First,
let's talk about some background information
on atherosclerosis. Atherosclerosis
refers to the thickening or hardening of the arteries caused
by a buildup of plaque.
Plaque is a fatty, waxy substance that forms deposits in
the artery walls.
Next,
let's take a look at the mechanism of the disease
by using a diagram to understand how it progresses over time.
Atherosclerosis begins with damage occurring
to the inner layer of the artery wall.
The layer is called the intima.
The intima is lined with endothelial cells, forming the endothelium.
The endothelium serves as a barrier between
the blood and the artery wall.
Damage to the endothelium can occur from high levels of
cholesterol,
various toxins, and high blood pressure for extended periods.
Once the damage occurs, cholesterol from the blood gathers
at the site and becomes oxidized
which triggers an immune response.
The immune response causes white blood cells to travel to
the area and form an inflammation.
Following this,
a fatty streak is one of the first visible signs
of the disease.
It is formed from dead cells at the injury site.
It is formed by the white blood cells,
also called monocytes,
turning into macrophages.
Macrophages will surround and kill any invading
cell. The macrophages will consume the cholesterol in this case
and become foam cells, which get their name from their
foamy appearance.
After the consumption of cholesterol, the foam cells will
die and more white blood cells are sent to the
area as a response.
This cycle continues and the endothelium is damaged even more.
The dead cells will form a bulge under
the endothelium, referred to as a fatty streak.
The process of forming more dead foam cells will continue
and other debris will continue building at the site of
the fatty streak, causing it to become a large piece
of plaque. The artery’s
smooth muscle cells with form a layer on top of the
plaque called a fibrous cap, which covers the plaque and
prevents it
from breaking off into the bloodstream.
The plaque continues to grow and can use calcium to
harden.
This growth will occur outward, restricting
blood flow
even more. Eventually the plaque will rupture.
This is done when the fibrous cap breaks open and
the plaque comes into contact with the blood.
This can cause a blood clot to form and will
block blood flow,
which can lead to a heart attack or stroke.
Let's move on to symptoms of atherosclerosis. Symptoms
may vary depending on which arteries are affected. The coronary
arteries supply blood to the heart. Symptoms of atherosclerosis in
the coronary arteries include angina,
which is chest pain,
shortness of breath,
and arrhythmias,
which is abnormal heartbeat.
The carotid arteries supply blood to the brain. Symptoms include
weakness,
paralysis or numbness in the face, arms, or legs, confusion,
breathing problems,
dizziness, and sudden and severe headache.
The peripheral arteries supply blood to the legs, arms, and
pelvis. Symptoms
include numbness and pain in those areas.
Lastly,
the renal arteries supply blood to the kidneys. Symptoms include
fatigue, changes
in how often you urinate, loss of appetite,
nausea, and itchiness or numbness.
There are some risk factors for atherosclerosis.
These may look familiar to many as the biggest risk
factor overall is being unhealthy.
Being overweight
can lead to increased risk for atherosclerosis. Also, old age
and diabetes
can be risk factors as well.
Some preventive measures
you can take to try and avoid this disease is
engaging in consuming a healthy diet,
engaging in physical activity,
and also not participating in smoking. Now that we have provided
an overview of atherosclerosis,
let's talk about the immune
system's involvement.
Here are some of the key immune system players that
are involved in the disease.
Macrophages
are resident cells in the blood vessels
that get rid of disease-causing agents through a process called
phagocytosis.
These cells quite literally eat up the substance, which in
this case is the cholesterol. Helper
T cells are part of the adaptive immune system, and
they can recognize specific substances and are activated against them.
Once activated, these cells migrate to the area of injury
and help activate other cells to fight against the disease-
causing agent.
Finally, cytokines are small molecules that are released by white blood
cells to attract other white blood cells to the area
of injury.
Let’s once again,
look at what's happening in the blood vessel. Low density
lipoproteins (or LDLs)
are small fatty proteins
that circulate in the blood. When they accumulate under the
endothelial layer,
they become oxidized. This starts the immune
response by binding to
specialized receptors on macrophages.
These cells
then remove the LDLs by
phagocytosis.
In atherosclerosis,
LDL accumulation is often too much for the macrophages to
handle.
So, as a cry for help, they release cytokines
which cause inflammation to occur.
These cytokines leave a trail of breadcrumbs
for white blood cells
to follow to reach the site of inflammation,
in this case,
the arterial endothelium.
This is where the helper T cells come in.
They enter into the blood vessels and help activate other
immune cells that try to reduce the LDL accumulation.
Additionally,
T cells further increase the inflammation in the blood vessels.
Inflammation is the primary cause for the worsening of atherosclerosis
because it can lead to plaques being ruptured.
When this occurs, blood clots can form
and can lead to thrombosis,
which is the blocking of blood vessels.
Consequently,
there is a high risk for heart attacks and strokes
to occur.
Adaptive immune cells are highly involved in autoimmune conditions,
which are conditions
where your own body's immune cells are attacking healthy
cells.
It can be seen that the recruitment of helper T
cells that attack your own body’s endothelium causes an
autoimmune reaction.
Thus, it can be said that atherosclerosis
is a kind of autoimmune condition.
There are a few treatments that we will talk about in
the video.
The first being cardiac catheterization and angioplasty.
This is a surgical procedure where they ploy a stent,
which is like a little balloon on a string, through
the femoral artery in your leg up into the affected
artery.
They then inflate that balloon,
causing the blood to have more room to flow through
the artery.
The second idea I want to talk about
has to do with the immune system.
So B1 lymphocytes are cells that our immune system
makes, and these cells
actually help prevent atherosclerosis.
But B2 lymphocytes actually make this condition worse because they
recruit lots of immune cells to the site of blockage
which then causes more blockage.
So there is ongoing research about how to tweak the immune system
in increasing B1 lymphocytes but not B2.
So now you can see that atherosclerosis,
a disease largely thought of as just a
heart condition, is so much more than that;
it is also an autoimmune disease.
Through this video,
we hope that you have gained some valuable insight on
atherosclerosis and can appreciate how the immune system
plays a part in diseases
such as this.
Thank you for watching and be sure to subscribe to
Demystifying Medicine McMaster!