Basic Response to Vascular Injury

00:01 Welcome back.

00:03 We're going to talk about kind of the stereotype way that vessels respond to injury.

00:08 Vessels of the cardiovascular system are pretty much one-trick ponies.

00:13 They know how to heal themselves.

00:15 But it may not always be the best and most adaptive way to heal.

00:20 They will not leak they will be fixed, but they may end up causing an overall obstruction to the lumen and restrict blood flow.

00:30 But if we understand this, then we will pretty much understand how every vessel responds to every sort of injury.

00:38 On the left hand side, we have a whole list of injuries not otherwise specified.

00:44 High blood pressure, high lipids, diabetes, cigarette smoke, vasculitis, that is to say inflammation, thrombosis.

00:53 Trauma, putting in a stent is traumatic, and dot, dot, dot.

00:57 There are a variety of ways that vessels can be injured, but they all respond in a very stereotyped way.

01:04 On the right hand side we have a vessel, a typical prototypical vessel with endothelial cells sitting on a basement membrane or basal membrane.

01:14 And beneath that smooth muscle cells of the media.

01:18 There will be an internal elastic lamina demarcating the intima, that is to say, the basement membrane and the endothelium from the media.

01:25 Alright, let's do evilness to it.

01:28 And the evilness is not otherwise specified, it can be any various forms of injury.

01:33 But basically, we are going to traumatize in various ways, the endothelial cells.

01:40 When they get traumatized, they will undergo various degrees of either destruction and dying, or they will become dysfunctional.

01:49 In many cases, we may not even lose endothelium, but they won't be them their normal selves, they will become procoagulant, they will become pro inflammatory.

01:59 So here, we've destroyed the endothelial cells in one form of injury.

02:04 And we have underlying tissue necrosis and injury as well.

02:08 Okay.

02:09 Because we no longer have an intact endothelium, we will get a platelet fibrin thrombus that's associated with it.

02:18 Keep in mind, you don't have to destroy the endothelium to have this happen as well.

02:22 We can have recruitment of platelets, recruitment of inflammatory cells, even on intact endothelium, provided they are sufficiently dysfunctional.

02:32 Here we have our thrombus.

02:34 Okay, that's fine.

02:36 But there are going to be a variety of mediators made by platelets, made by the inflammatory cells, and made by the dysfunctional endothelium that's growing in and that's going to recruit and activate additional inflammatory cells and recruit and activate smooth muscle cells from the media, that will traipse into the intima.

02:56 The idea is, we're trying to heal damage to the vessel.

03:00 And the only way we have it, to do it is we don't put fibroblasts in there, per se, we put in smooth muscle cells.

03:07 The smooth muscle cells that come in, have a different phenotype than where they came from.

03:12 So in the media, smooth muscle cells are mainly contractile, they don't proliferate very much at all.

03:19 And they don't make a whole lot of matrix.

03:21 However, when we recruit them and activate them into this intimal lesion, those cells now are going to be very proliferative.

03:32 They're going to make a lot of matrix and they won't contract very well.

03:36 So they're undergo of phenotypic change, that's going to be important for healing the lesion to the vessel wall.

03:43 But as you can see in here, we've compromised blood flow.

03:47 So the cells that are in there now are motile, they've become very active and they have grown in by Chemokinesis.

03:55 They are non contractile.

03:57 They respond to cytokines and growth factors by making more of themselves and by synthesizing a lot of matrix.

04:03 With time, that intimal hyperplasia can remodel.

04:07 But if we have recurrent bouts of injury, or we have significant injury to begin with, you may end up with a permanent partial or even near complete occlusion of the vessel lumen.

04:19 In larger bore vessels, not a big deal.

04:22 So in the aorta when this happens, we're okay more or less.

04:26 We'll talk about other diseases of the aorta later.

04:29 But, in a small-bore vessel like a coronary artery, it's a big deal.

04:34 So if you have intimal proliferation, that includes smooth muscle cells, and matrix and necrotic debris, that's atherosclerosis, and that atherosclerosis part of the normal healing of a vessel that's been injured can be significant in terms of the amount of occlusion of flow.

04:54 Okay, we've seen now the steps of the way that a vessel wall responds to injury.

05:01 And it kind of makes sense, but let's see what happens kind of live time with a video.

05:06 And this will be a great way to review some of the major steps.

05:11 Okay, so now we have our vessel with our intima intact endothelial cells minding their own business going about their lives very happy.

05:20 Cells are flowing down the lumen from left to right.

05:23 And then life happens, injury occurs, and the endothelial cells become either non functional, dysfunctional or outright die.

05:31 Oh my goodness, now we have an injury to the vessel wall that we need to heal so we don't bleed.

05:37 In doing so we're going to lay down and recruit platelets.

05:40 And we're also going to recruit inflammatory cells that stick as part of that.

05:46 We're going to cement the whole gemish together with fibrin.

05:51 And now those inflammatory cells in those platelets will recruit and activate inflammatory cells.

05:57 Here we see lymphocytes and monocytes coming in, which will make cytokines, that little blue dots, that little red dots, those cytokines are going to induce the recruitment and activation of smooth muscle cells coming from the media.

06:09 Those smooth muscle cells now are proliferative and they make matrix they're non contractile and those are going to heal our wound.

06:18 Okay, this is how we heal the vessel injury.

06:21 But they're also as you can see there, going to lead to partial luminal obstruction, and it may remodel ever so slightly, but if we have recurrent injury, or we have significant injury to begin with, it's going to lead to a significant vascular obstruction.

06:40 That's what atherosclerosis is, but any injury to a vessel wall, it's this kind of response.