[Script Info]
Title: 
[Events]
Format: Layer, Start, End, Style, Name, MarginL, MarginR, MarginV, Effect, Text
Dialogue: 0,0:00:00.00,0:00:01.88,Default,,0000,0000,0000,,
Dialogue: 0,0:00:01.88,0:00:04.04,Default,,0000,0000,0000,,I'm actually just going\Nto take a step back,
Dialogue: 0,0:00:04.04,0:00:06.36,Default,,0000,0000,0000,,clear out some of this stuff.
Dialogue: 0,0:00:06.36,0:00:09.38,Default,,0000,0000,0000,,You've understood\Nthe first half of how
Dialogue: 0,0:00:09.38,0:00:14.12,Default,,0000,0000,0000,,this process of\Natherosclerosis happens.
Dialogue: 0,0:00:14.12,0:00:17.08,Default,,0000,0000,0000,,And we're going to finish\Noff the second half.
Dialogue: 0,0:00:17.08,0:00:19.75,Default,,0000,0000,0000,,So all of the action\Nis still going
Dialogue: 0,0:00:19.75,0:00:21.34,Default,,0000,0000,0000,,to happen in the tunica intima.
Dialogue: 0,0:00:21.34,0:00:24.07,Default,,0000,0000,0000,,So that much is going\Nto stay the same.
Dialogue: 0,0:00:24.07,0:00:25.74,Default,,0000,0000,0000,,And so far, we talked\Nabout macrophages.
Dialogue: 0,0:00:25.74,0:00:28.69,Default,,0000,0000,0000,,And we talked about how\Nthey form foam cells
Dialogue: 0,0:00:28.69,0:00:32.52,Default,,0000,0000,0000,,and they eat up all\Nthe fat and they
Dialogue: 0,0:00:32.52,0:00:35.13,Default,,0000,0000,0000,,form this kind of lake of fat.
Dialogue: 0,0:00:35.13,0:00:37.63,Default,,0000,0000,0000,,And so let me leave it there.
Dialogue: 0,0:00:37.63,0:00:39.70,Default,,0000,0000,0000,,So that's where the\Npicture's at so far.
Dialogue: 0,0:00:39.70,0:00:43.09,Default,,0000,0000,0000,,And now let's talk about\Nwhat happens after that.
Dialogue: 0,0:00:43.09,0:00:48.70,Default,,0000,0000,0000,,So the next step,\Nstep five, basically
Dialogue: 0,0:00:48.70,0:00:50.93,Default,,0000,0000,0000,,what happens is the\Nsmooth muscle cells--
Dialogue: 0,0:00:50.93,0:00:52.97,Default,,0000,0000,0000,,smooth muscle cells, we\Nhaven't talked about them
Dialogue: 0,0:00:52.97,0:01:01.93,Default,,0000,0000,0000,,so far-- they shimmy,\Nor they dance over.
Dialogue: 0,0:01:01.93,0:01:08.65,Default,,0000,0000,0000,,Let's write dance\Nover to tunica intima.
Dialogue: 0,0:01:08.65,0:01:11.61,Default,,0000,0000,0000,,So really, again, everything is\Nhappening in the tunica intima,
Dialogue: 0,0:01:11.61,0:01:12.11,Default,,0000,0000,0000,,right?
Dialogue: 0,0:01:12.11,0:01:12.87,Default,,0000,0000,0000,,You can see that.
Dialogue: 0,0:01:12.87,0:01:14.16,Default,,0000,0000,0000,,That's where all the action is.
Dialogue: 0,0:01:14.16,0:01:15.78,Default,,0000,0000,0000,,And so when I say\Nthey dance over,
Dialogue: 0,0:01:15.78,0:01:17.31,Default,,0000,0000,0000,,I'm being a little bit silly.
Dialogue: 0,0:01:17.31,0:01:19.46,Default,,0000,0000,0000,,But basically, what happens\Nis that these cells,
Dialogue: 0,0:01:19.46,0:01:24.21,Default,,0000,0000,0000,,these red, smooth muscle cells--\Nthese are the smooth muscle
Dialogue: 0,0:01:24.21,0:01:30.64,Default,,0000,0000,0000,,cells-- they are going\Nto start migrating.
Dialogue: 0,0:01:30.64,0:01:33.22,Default,,0000,0000,0000,,They're going to start\Nmigrating or moving.
Dialogue: 0,0:01:33.22,0:01:35.73,Default,,0000,0000,0000,,And they're going to start\Nmigrating into this space.
Dialogue: 0,0:01:35.73,0:01:37.54,Default,,0000,0000,0000,,Maybe that one\Nwill go over there.
Dialogue: 0,0:01:37.54,0:01:40.92,Default,,0000,0000,0000,,Maybe this one will go over\Nhere, perhaps this one.
Dialogue: 0,0:01:40.92,0:01:42.78,Default,,0000,0000,0000,,And the way they\Nstart migrating is
Dialogue: 0,0:01:42.78,0:01:45.01,Default,,0000,0000,0000,,that there's a lot\Nof action going on.
Dialogue: 0,0:01:45.01,0:01:46.16,Default,,0000,0000,0000,,The macrophages are there.
Dialogue: 0,0:01:46.16,0:01:49.50,Default,,0000,0000,0000,,They've got the LDL\Nin that lake of fat.
Dialogue: 0,0:01:49.50,0:01:52.35,Default,,0000,0000,0000,,And a lot of chemicals are\Nbeing released by these cells.
Dialogue: 0,0:01:52.35,0:01:54.79,Default,,0000,0000,0000,,And so they sense that\Nsomething's happening.
Dialogue: 0,0:01:54.79,0:01:56.34,Default,,0000,0000,0000,,So they kind of move over there.
Dialogue: 0,0:01:56.34,0:02:01.56,Default,,0000,0000,0000,,And what they begin to\Ndo is make a fibrous cap.
Dialogue: 0,0:02:01.56,0:02:03.57,Default,,0000,0000,0000,,That's step six.
Dialogue: 0,0:02:03.57,0:02:07.09,Default,,0000,0000,0000,,So they make a fibrous cap.
Dialogue: 0,0:02:07.09,0:02:10.31,Default,,0000,0000,0000,,Actually, let me write who\Nmakes it, so it's very clear.
Dialogue: 0,0:02:10.31,0:02:15.06,Default,,0000,0000,0000,,Smooth muscle cells,\NS-M-C, smooth muscle cells
Dialogue: 0,0:02:15.06,0:02:18.01,Default,,0000,0000,0000,,make a fibrous cap.
Dialogue: 0,0:02:18.01,0:02:20.40,Default,,0000,0000,0000,,And what a fibrous\Ncap is is think
Dialogue: 0,0:02:20.40,0:02:21.77,Default,,0000,0000,0000,,about when you\Nwere really young.
Dialogue: 0,0:02:21.77,0:02:22.64,Default,,0000,0000,0000,,And you were playing.
Dialogue: 0,0:02:22.64,0:02:25.61,Default,,0000,0000,0000,,And you didn't really pay\Nattention and fell a lot.
Dialogue: 0,0:02:25.61,0:02:27.95,Default,,0000,0000,0000,,You might have come\Nhome with skinned knees.
Dialogue: 0,0:02:27.95,0:02:28.79,Default,,0000,0000,0000,,And I certainly did.
Dialogue: 0,0:02:28.79,0:02:31.23,Default,,0000,0000,0000,,And my mom used to\Nalways remark on that.
Dialogue: 0,0:02:31.23,0:02:34.98,Default,,0000,0000,0000,,And those skinned knees\Nturn into scabs, right?
Dialogue: 0,0:02:34.98,0:02:38.54,Default,,0000,0000,0000,,And so these smooth muscle\Ncells, these fibrous caps,
Dialogue: 0,0:02:38.54,0:02:42.45,Default,,0000,0000,0000,,basically think of\Nit as a scab, a scab
Dialogue: 0,0:02:42.45,0:02:47.19,Default,,0000,0000,0000,,that forms over\Nthis lake of fat.
Dialogue: 0,0:02:47.19,0:02:50.49,Default,,0000,0000,0000,,So I've been drawing for\Nyou this yellow lake of fat.
Dialogue: 0,0:02:50.49,0:02:52.27,Default,,0000,0000,0000,,And now these\Nsmooth muscle cells,
Dialogue: 0,0:02:52.27,0:02:54.64,Default,,0000,0000,0000,,they come in and\Nsay, well, we've
Dialogue: 0,0:02:54.64,0:02:59.05,Default,,0000,0000,0000,,got to make a cap\Nover this thing.
Dialogue: 0,0:02:59.05,0:03:02.88,Default,,0000,0000,0000,,Let me erase again and draw for\Nyou what that might look like.
Dialogue: 0,0:03:02.88,0:03:06.61,Default,,0000,0000,0000,,So let's say that this\Nlake is getting bigger.
Dialogue: 0,0:03:06.61,0:03:09.90,Default,,0000,0000,0000,,This lake, over time, has\Ngotten really quite big.
Dialogue: 0,0:03:09.90,0:03:14.06,Default,,0000,0000,0000,,And you've got more fat in\Nhere from all that LDL that
Dialogue: 0,0:03:14.06,0:03:16.80,Default,,0000,0000,0000,,keeps depositing,\Nbecause, going backwards,
Dialogue: 0,0:03:16.80,0:03:19.51,Default,,0000,0000,0000,,the endothelial cells\Nare not working well.
Dialogue: 0,0:03:19.51,0:03:23.07,Default,,0000,0000,0000,,And so you've got\Nthis kind of weird set
Dialogue: 0,0:03:23.07,0:03:26.48,Default,,0000,0000,0000,,of endothelium\Nkind of around it.
Dialogue: 0,0:03:26.48,0:03:31.22,Default,,0000,0000,0000,,And the smooth muscle\Ncells come over,
Dialogue: 0,0:03:31.22,0:03:34.79,Default,,0000,0000,0000,,and they decide they're going to\Nhelp with making a fibrous cap.
Dialogue: 0,0:03:34.79,0:03:38.56,Default,,0000,0000,0000,,So let me do that\Nin a new color.
Dialogue: 0,0:03:38.56,0:03:39.86,Default,,0000,0000,0000,,Let's do it in red.
Dialogue: 0,0:03:39.86,0:03:41.67,Default,,0000,0000,0000,,I guess that would\Ncome up nicely.
Dialogue: 0,0:03:41.67,0:03:46.32,Default,,0000,0000,0000,,So they basically\Nmake this cap here.
Dialogue: 0,0:03:46.32,0:03:53.01,Default,,0000,0000,0000,,And this cap mixes in to this\Nlayer and settles in right
Dialogue: 0,0:03:53.01,0:03:55.12,Default,,0000,0000,0000,,there, right?
Dialogue: 0,0:03:55.12,0:03:58.01,Default,,0000,0000,0000,,And you've got some\Nendothelium over it,
Dialogue: 0,0:03:58.01,0:03:59.78,Default,,0000,0000,0000,,but sometimes you don't.
Dialogue: 0,0:03:59.78,0:04:03.96,Default,,0000,0000,0000,,And so this layer of endothelium\Nis pretty well disrupted,
Dialogue: 0,0:04:03.96,0:04:04.89,Default,,0000,0000,0000,,I would say.
Dialogue: 0,0:04:04.89,0:04:07.35,Default,,0000,0000,0000,,You've got this nice,\Nthick fibrous cap.
Dialogue: 0,0:04:07.35,0:04:11.74,Default,,0000,0000,0000,,And what's in that cap is things\Nlike collagen, or elastin.
Dialogue: 0,0:04:11.74,0:04:14.12,Default,,0000,0000,0000,,So proteins are in this cap.
Dialogue: 0,0:04:14.12,0:04:18.47,Default,,0000,0000,0000,,So you've got a fibrous cap.
Dialogue: 0,0:04:18.47,0:04:25.66,Default,,0000,0000,0000,,And it's made of\Ncollagen and elastin.
Dialogue: 0,0:04:25.66,0:04:27.54,Default,,0000,0000,0000,,So these are the\Nproteins that we
Dialogue: 0,0:04:27.54,0:04:33.24,Default,,0000,0000,0000,,know help with keeping all of\Nthe cells in our body in place.
Dialogue: 0,0:04:33.24,0:04:36.45,Default,,0000,0000,0000,,And so you can always point\Nto your bones, or your nose,
Dialogue: 0,0:04:36.45,0:04:38.89,Default,,0000,0000,0000,,and you can find\Nthese proteins there.
Dialogue: 0,0:04:38.89,0:04:40.93,Default,,0000,0000,0000,,So it makes this fibrous cap.
Dialogue: 0,0:04:40.93,0:04:46.70,Default,,0000,0000,0000,,And so now, really, what\Nyou have is fat with a cap.
Dialogue: 0,0:04:46.70,0:04:48.76,Default,,0000,0000,0000,,So that's kind of\Nhow I think of this.
Dialogue: 0,0:04:48.76,0:04:55.02,Default,,0000,0000,0000,,This is fat with a cap.
Dialogue: 0,0:04:55.02,0:04:56.53,Default,,0000,0000,0000,,And it sounds simple.
Dialogue: 0,0:04:56.53,0:04:59.27,Default,,0000,0000,0000,,And in a way, that's a very\Nreasonable way to think of it.
Dialogue: 0,0:04:59.27,0:05:01.43,Default,,0000,0000,0000,,You've got the lake of fat.
Dialogue: 0,0:05:01.43,0:05:03.97,Default,,0000,0000,0000,,And over it, you've\Ngot this fibrous cap.
Dialogue: 0,0:05:03.97,0:05:06.39,Default,,0000,0000,0000,,And what that does\Nis two things.
Dialogue: 0,0:05:06.39,0:05:07.93,Default,,0000,0000,0000,,You've already seen\Nthat this is kind
Dialogue: 0,0:05:07.93,0:05:11.24,Default,,0000,0000,0000,,of starting to bulge into\Nthe blood vessel, right?
Dialogue: 0,0:05:11.24,0:05:13.70,Default,,0000,0000,0000,,I'm going to go to that little\Ndiagram in the corner again.
Dialogue: 0,0:05:13.70,0:05:16.85,Default,,0000,0000,0000,,So you had a beautiful\Nblood vessel, nice and kind
Dialogue: 0,0:05:16.85,0:05:18.67,Default,,0000,0000,0000,,of circular.
Dialogue: 0,0:05:18.67,0:05:21.64,Default,,0000,0000,0000,,And then, now,\Nyou've got this fat
Dialogue: 0,0:05:21.64,0:05:26.91,Default,,0000,0000,0000,,that's sitting in here,\Nthis giant lake, right?
Dialogue: 0,0:05:26.91,0:05:29.76,Default,,0000,0000,0000,,And over it, I put a cap.
Dialogue: 0,0:05:29.76,0:05:32.08,Default,,0000,0000,0000,,So now you've got a cap here.
Dialogue: 0,0:05:32.08,0:05:33.83,Default,,0000,0000,0000,,So what has happened\Nto this blood vessel?
Dialogue: 0,0:05:33.83,0:05:37.99,Default,,0000,0000,0000,,Well, you had a certain\Nradius on that blood vessel.
Dialogue: 0,0:05:37.99,0:05:41.11,Default,,0000,0000,0000,,And that radius\Nhas gotten smaller.
Dialogue: 0,0:05:41.11,0:05:49.36,Default,,0000,0000,0000,,So in terms of big key\Nideas, key changes,
Dialogue: 0,0:05:49.36,0:05:53.20,Default,,0000,0000,0000,,your blood vessel has\Nactually gotten smaller.
Dialogue: 0,0:05:53.20,0:05:57.49,Default,,0000,0000,0000,,So one is smaller radius.
Dialogue: 0,0:05:57.49,0:05:59.28,Default,,0000,0000,0000,,And you can see that\Nin the picture, right?
Dialogue: 0,0:05:59.28,0:06:01.18,Default,,0000,0000,0000,,Smaller radius.
Dialogue: 0,0:06:01.18,0:06:04.80,Default,,0000,0000,0000,,And we know that radius\Nis related to resistance.
Dialogue: 0,0:06:04.80,0:06:08.08,Default,,0000,0000,0000,,So that means\Nincreased resistance.
Dialogue: 0,0:06:08.08,0:06:12.50,Default,,0000,0000,0000,,Increased resistance\Nhere to blood flow.
Dialogue: 0,0:06:12.50,0:06:16.31,Default,,0000,0000,0000,,And of course, I'm talking\Nabout the distance from here
Dialogue: 0,0:06:16.31,0:06:19.43,Default,,0000,0000,0000,,over to here is smaller, now\Nthat you've got something
Dialogue: 0,0:06:19.43,0:06:22.43,Default,,0000,0000,0000,,pooching out into the lumen.
Dialogue: 0,0:06:22.43,0:06:24.54,Default,,0000,0000,0000,,And the other change--\Nand this is actually
Dialogue: 0,0:06:24.54,0:06:28.11,Default,,0000,0000,0000,,quite interesting-- is\Nthat the wall itself
Dialogue: 0,0:06:28.11,0:06:30.17,Default,,0000,0000,0000,,is actually tougher.
Dialogue: 0,0:06:30.17,0:06:31.87,Default,,0000,0000,0000,,It's more stiff.
Dialogue: 0,0:06:31.87,0:06:34.81,Default,,0000,0000,0000,,And so right here, one\Nof the other things--
Dialogue: 0,0:06:34.81,0:06:37.05,Default,,0000,0000,0000,,actually, I didn't\Ntalk about it much,
Dialogue: 0,0:06:37.05,0:06:39.64,Default,,0000,0000,0000,,but maybe I should say very\Nquickly right now-- maybe even
Dialogue: 0,0:06:39.64,0:06:46.65,Default,,0000,0000,0000,,a step seven is that the smooth\Nmuscle cells make-- or let's
Dialogue: 0,0:06:46.65,0:06:53.69,Default,,0000,0000,0000,,say here-- lay down calcium.
Dialogue: 0,0:06:53.69,0:06:56.42,Default,,0000,0000,0000,,So when I say lay down,\Nwhat does that mean exactly?
Dialogue: 0,0:06:56.42,0:06:58.36,Default,,0000,0000,0000,,Are they like bricklayers?
Dialogue: 0,0:06:58.36,0:07:00.19,Default,,0000,0000,0000,,But when I say lay down\Ncalcium, what I mean
Dialogue: 0,0:07:00.19,0:07:03.53,Default,,0000,0000,0000,,is that these cells\Nare actually going
Dialogue: 0,0:07:03.53,0:07:07.90,Default,,0000,0000,0000,,to start pretending in a way\Nthat they are making bone.
Dialogue: 0,0:07:07.90,0:07:10.43,Default,,0000,0000,0000,,And actually, the\Ndead foam cells
Dialogue: 0,0:07:10.43,0:07:13.86,Default,,0000,0000,0000,,create this little\Nmicro-environment
Dialogue: 0,0:07:13.86,0:07:17.10,Default,,0000,0000,0000,,where these smooth muscles start\Nthinking, oh, my gosh, maybe I
Dialogue: 0,0:07:17.10,0:07:19.38,Default,,0000,0000,0000,,should lay down some calcium,\Nput some calcium here.
Dialogue: 0,0:07:19.38,0:07:22.33,Default,,0000,0000,0000,,So they'll put a little\Ncalcium nugget right here.
Dialogue: 0,0:07:22.33,0:07:24.84,Default,,0000,0000,0000,,I'll put another calcium\Nnugget right there.
Dialogue: 0,0:07:24.84,0:07:28.22,Default,,0000,0000,0000,,And I'll put another calcium\Nnugget there and there.
Dialogue: 0,0:07:28.22,0:07:30.41,Default,,0000,0000,0000,,And all of a sudden,\Nif you start looking,
Dialogue: 0,0:07:30.41,0:07:32.21,Default,,0000,0000,0000,,you start thinking,\Noh, wow, this
Dialogue: 0,0:07:32.21,0:07:34.95,Default,,0000,0000,0000,,is actually very calcified.
Dialogue: 0,0:07:34.95,0:07:40.21,Default,,0000,0000,0000,,And this is actually looking\Na little bit like bone.
Dialogue: 0,0:07:40.21,0:07:42.56,Default,,0000,0000,0000,,This is what happens with bone.
Dialogue: 0,0:07:42.56,0:07:45.62,Default,,0000,0000,0000,,So they start calcifying\Nthis entire area.
Dialogue: 0,0:07:45.62,0:07:49.62,Default,,0000,0000,0000,,And if you calcify this area,\Nif you start putting down
Dialogue: 0,0:07:49.62,0:07:51.70,Default,,0000,0000,0000,,these little\Ncrystals of calcium,
Dialogue: 0,0:07:51.70,0:07:54.97,Default,,0000,0000,0000,,then what's going to happen is\Nthat your arteries literally
Dialogue: 0,0:07:54.97,0:07:59.94,Default,,0000,0000,0000,,become crispy, crunchy, which\Nsounds kind of disgusting.
Dialogue: 0,0:07:59.94,0:08:01.15,Default,,0000,0000,0000,,I guess it is.
Dialogue: 0,0:08:01.15,0:08:04.10,Default,,0000,0000,0000,,But they're\Nessentially more stiff.
Dialogue: 0,0:08:04.10,0:08:05.56,Default,,0000,0000,0000,,And that's really\Nthe key point, is
Dialogue: 0,0:08:05.56,0:08:10.84,Default,,0000,0000,0000,,that you get more stiffness,\Nor lower compliance.
Dialogue: 0,0:08:10.84,0:08:16.28,Default,,0000,0000,0000,,
Dialogue: 0,0:08:16.28,0:08:21.47,Default,,0000,0000,0000,,And that goes back to the\Ncrunchiness of the vessel,
Dialogue: 0,0:08:21.47,0:08:24.51,Default,,0000,0000,0000,,or the inability to\Nbe kind of flexible.
Dialogue: 0,0:08:24.51,0:08:30.91,Default,,0000,0000,0000,,So lower compliance,\Nless flexible.
Dialogue: 0,0:08:30.91,0:08:34.30,Default,,0000,0000,0000,,Just as a little reminder\Nof what that means.
Dialogue: 0,0:08:34.30,0:08:36.21,Default,,0000,0000,0000,,So those are the big\Nchanges that you see.
Dialogue: 0,0:08:36.21,0:08:39.78,Default,,0000,0000,0000,,And the lower radius\Nincreases resistance.
Dialogue: 0,0:08:39.78,0:08:42.61,Default,,0000,0000,0000,,And the lower compliance\Nmeans that it's
Dialogue: 0,0:08:42.61,0:08:45.77,Default,,0000,0000,0000,,harder for these large\Nand middle-sized arteries
Dialogue: 0,0:08:45.77,0:08:50.05,Default,,0000,0000,0000,,to expand like a balloon every\Ntime the blood pulses through.
Dialogue: 0,0:08:50.05,0:08:54.54,Default,,0000,0000,0000,,So both those things are\Ngoing to cause increase
Dialogue: 0,0:08:54.54,0:08:56.59,Default,,0000,0000,0000,,in your blood pressure.
Dialogue: 0,0:08:56.59,0:08:58.63,Default,,0000,0000,0000,,