00:01
So, we've had Factor 1.
00:02
Remember that was
interferon gamma.
00:04
Factor 2: 2 for interleukin-1
and TNF, Tumor Necrosis Factor.
00:08
Factor 3: Epidermal Growth Factor.
00:11
Realizing there a whole
bunch of growth factors.
00:13
Factor 4A, is going to be our
Basic Fibroblast Growth Factor.
00:18
And on the next slide,
Factor 4B is going to be VEGF.
00:21
So we're going to have
kind of two Factor 4s.
00:26
This and VEGF mediate all the
activities for angiogenesis.
00:30
Everything you need,
except that maturation step,
it's synthesized by macrophages.
00:35
It's synthesized
interestingly enough,
by endothelial cells
and smooth muscle cells as well.
00:40
So again, another example
of a feed-forward autocrine loop.
00:45
It's very potent, endothelial cell
and some muscle cell
chemokine and mitogens.
00:50
So it drives not only
the movement in migration,
but also the proliferation
that's what mitogen means.
00:56
And induces remodeling
of the basement membrane
and the extracellular matrix,
that's how we got
the original sprout.
01:02
And remember, it's sitting out
there in the matrix all the time.
01:07
It is made by macrophages,
and it's sitting in the matrix
and we have to
cleave it away from heparin
in order for it
to have an effect.
01:14
Okay, VEGF.
01:17
So this induces angiogenesis.
01:19
It also increases
that vascular permeability.
01:22
In fact, in some of the literature,
you may see it described as
vascular permeability factor.
01:27
What's in a name, right?
It's synthesized by activated
macrophages by epithelial cells,
and interestingly by tumor cells.
01:34
We'll come back to this
when we talk about cancer,
because tumor cells
being very clever and diabolical,
can actually help drive
the production of new blood vessels
to feed themselves
through the elaboration of VEGF,
and other angiogenic factors.
01:50
But for purposes of wound healing,
it's the activated macrophage
that we care about here.
01:55
So we've started to set the
stage for the final scarring
by having angiogenesis,
granulation tissue
which is not your grandma.