Atherosclerosis: Pathophysiology

00:00 Okay, another kind of general thing.

00:04 So, by way of a summary, wound healing is a very stereotyped response to injury.

00:11 You get tissue injury, we get our initial inflammatory cell recruitment and activation.

00:19 They elaborate cytokines and growth factors.

00:21 We get angiogenesis, if we can't restore normal function, we form scar, starting with angiogenesis.

00:29 We get proliferation of the fibroblasts that are going to lay down more matrix.

00:35 And we remodel that matrix.

00:38 And this is what happens when we can't regenerate.

00:42 Obviously, if we can regenerate, we get complete renewal, we don't have those last three steps.

00:47 Okay, that stereotype response actually happens over, and over, and over again, in different disguises throughout the body.

00:56 This is, by way of an early introduction.

00:59 In a subsequent set of topics that we're going to share together can't wait.

01:05 We're gonna talk about atherosclerosis, which is a major form of human disease.

01:09 50% of the people listening to me, will die as a result of atherosclerosis.

01:15 Whoa, and any of that.

01:18 The point here is a little bit of an appetizer for the main course that will do much later, is that atherosclerosis is actually fundamentally response to vascular injury or vascular wounding.

01:30 And that's what atherosclerosis is.

01:32 It's the healing response in a blood vessel.

01:36 It's the same process. It's exactly the same process.

01:39 So there's not anything particularly new to learn about atherosclerosis except some of the names.

01:44 So in any event, we have some initial injury.

01:47 That initial injury are the risk factors.

01:50 Can be infection, but it's hypertension, it's smoking, it's diabetes, it's hypercholesterolemia, there can be genetic factors.

01:56 There can be inflammation, that's the tissue injury.

02:00 And then we recruit in because of tissue injury, inflammatory cells, lymphocytes and macrophages.

02:05 And they get activated.

02:06 And they're making chemokines and huge molecules, and they're making interferon gamma.

02:10 They're doing all the things that we've talked about.

02:14 They are also elaborating interleukin-1 and TNF, the macrophages in particular, which will drive the recruitment and activation of smooth muscle cells that live in the media, and will drive angiogenesis.

02:26 So we will get everything we've talked about and wound healing going on in this vessel wall.

02:32 With cellular proliferation, coming from a variety of other factors, TGF-beta other things, we will get now the smooth muscle cells that had been recruited to proliferate, and we get a progressive increase in plaque formation.

02:49 It's just the vessel responding to injury.

02:52 It will make more matrix.

02:54 So we'll get a lot more collagen that's in there.

02:57 Again, driven by the same factors we've been talking about.

03:00 And that matrix, it remodels.

03:03 And when remodels with matrix metalloproteinases, we can get a plaque rupture, and we get a plaque rupture and then we get a thrombus.

03:10 And that's an acute heart attack right there happening if this is a coronary artery.

03:15 So this is an appetizer again for the main course that we'll talk about later.

03:18 But basically, atherosclerosis is just response of the vessel wall to injury.

03:26 Here's what it looks like histologically.

03:28 This is a coronary artery, and you're looking at the cause of death in this patient.

03:34 The darker pink rim kind of all the way around at the periphery of that is smooth muscle media.

03:41 Everything that's inside of that, that looks kind of blue and different colors, that's atherosclerotic plaque.

03:50 And then that pink thing in the middle is where the plaque ruptured, and we have an acute thrombus.

03:57 So you're looking at the cause of death, but we're basically looking at 20 years, 30 years of vessel wall injury, and normal wound healing in a vessel.