Atherosclerosis: Pathophysiology

by Richard Mitchell, MD, PhD

My Notes
  • Required.
Save Cancel
    Learning Material 2
    • PDF
      Slides Acute and Chronic Inflammation Complications of healing.pdf
    • PDF
      Download Lecture Overview
    Report mistake

    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.

    About the Lecture

    The lecture Atherosclerosis: Pathophysiology by Richard Mitchell, MD, PhD is from the course Acute and Chronic Inflammation.

    Included Quiz Questions

    1. Matrix metalloproteinase (MMP)
    2. Lipase
    3. Hydrogen peroxidase
    4. Amylase
    5. Hyaluronidase
    1. Tumor necrosis factor-alpha (TNF-α)
    2. IL-5
    3. IL-8
    4. IL-6
    5. Interferon-gamma (IFN-γ)

    Author of lecture Atherosclerosis: Pathophysiology

     Richard Mitchell, MD, PhD

    Richard Mitchell, MD, PhD

    Customer reviews

    5,0 of 5 stars
    5 Stars
    4 Stars
    3 Stars
    2 Stars
    1  Star