00:02
Okay,
so, to recapitulate once again,
atherosclerosis is a stereotype
vascular response to injury.
00:14
And that's what's shown
on the left hand side,
it's got the traditional
risk factors,
hypertension,
hypercholesterolemia, diabetes,
smoking, genetics.
00:22
It's a cause of death in roughly
a quarter of the US population.
00:26
Okay,
that's atherosclerosis,
but intimal proliferation,
such you see an atherosclerosis,
that accumulation of smooth
muscle cells in matrix
is also part and parcel of
every injury to an artery.
00:41
And there are other forms
of injury to arteries.
00:43
So keep that in mind when you're
dealing with your patients.
00:46
So in transplanted hearts
or transplanted any organ,
there is going to be an
ongoing immune response.
00:57
That will cause progressive
intimal stenosis
due to smooth muscle
cell proliferation,
and elaboration of
extracellular matrix
that becomes significant
limiting in terms of flow
in 50% of patients
within five years.
01:12
So that's graphed
arterial disease,
again, injury of a different
form immune mediated injury,
as opposed to
something driven by
the inflammation that goes
on with hypercholesterolemia,
or endothelial cell dysfunction.
01:27
And when we do stents,
so this is a stented vessel.
01:31
The areas that are
highlighted in the box
with the kind of a clearing,
represent where the
stent struts were,
that caused local trauma.
01:40
There was also local thrombosis
combination of the trauma and thrombosis
is injury to the endothelium.
01:46
And the same
stereotype responses
to vascular injury
are at play here.
01:52
So we get a concentric
intimal hyperplasia,
and 20 to 30% of stents
because of this healing
process within the intima,
will stenose every year.
02:04
So vessels are kind
of one trick pony,
is they can only
respond a certain way
when they get injured
and they get injured
in different ways you
see on this slide.
02:14
Their only response is to
have intimal proliferation.
02:18
With more smooth muscle
cell recruitment,
and more matrix production.
02:25
Let's delve into one other
aspect of atherosclerosis.
02:29
So aneurysm formation,
due to the production
of proteases
by the recruited
inflammatory cells.
02:38
This is a big deal.
02:38
So we're looking on the
right hand side and an aorta.
02:41
The branches on either
side we are going to the,
are the renal arteries now
in the infrarenal location
just above the
iliac bifurcation.
02:50
There's a big globular swelling
that represents a weakening
a thing of the wall
and an out-pouching
of this aorta.
03:01
At that size,
it has a significant
risk of rupture.
03:05
So there's 3% prevalence
in the elderly population,
that is to say over 80 years old
3% of that population,
which is pretty significant,
will have abdominal,
aortic aneurysm or a triple A.
03:20
15,000 deaths per year occur in
the world as a result of rupture.
03:25
And it's, again, this aneurism, as for
me as a result of chronic inflammation,
loss of elastic tissue,
and increased matrix turnover
due to the inflammatory
cell recruitment
into these because of the
underlying atherosclerosis.
03:40
And predominantly,
there are certain cytokines,
T-helper cytokine, type two,
interleukin-4, interleukin-13,
that are driving this process.
03:50
So, think about this,
we can start with a vessel in the
little blue dots on this vessel
are inflammatory cells.
03:58
And if they produce
predominantly interferon gamma,
TH1 type cytokines,
we get intimal proliferation,
and that could be driving,
that could be atherosclerosis,
it could be transplant arteriopathy,
it could be stent restenosis.
04:14
On the other hand,
if the recruited inflammatory
cells make more TH2 cytokines
like interleukin-4,
we get the activation of
macrophages to make proteases
that will create an aneurysm.
04:28
So kind of two way path depending
on how things get activated.
04:33
With that we've looked at
different forms of plaque
and different responses
to different stimulation,
giving us the pathologies that
can happen with atherosclerosis.