General Concepts for Atherosclerosis and Myocardial Infarct

00:01 All right, as we've come to the conclusion of our many sessions together, which have been enjoyable for me on atherosclerosis and myocardial infarction, big picture points to take away.

00:14 So atherosclerosis is fundamentally a response to vessel wall injury.

00:19 The endothelial cells aren't irreversibly damaged.

00:22 They're still there, but they're dysfunctional.

00:26 If you remember the typical features of injury and wound healing in any other tissue, and apply it to a vessel wall, you understand all the elements of atherosclerosis.

00:39 Lesions of atherosclerosis, fortunately, in most of us, typically progress very slowly.

00:45 It requires decades before they become symptomatic.

00:49 So you will get progressive occlusion but then remember, there's remodeling, that lag off phenomena.

00:56 And so up to a point where you get about 70 percent occlusion, you may be completely asymptomatic, and then all heck breaks loose.

01:05 And you'll have events punctuated by sudden plaque rupture, thrombosis.

01:12 We reach a Rubicon, beyond which we now have completely limiting flow.

01:19 When we lose flow, when we don't have perfusion into a tissue, function is lost before viability.

01:25 The cells that are not being perfused, not getting oxygen, not getting nutrition, will try valiantly to keep alive for as long as they possibly can.

01:36 To do that, they will go to anaerobic glycolysis.

01:39 I'm sorry, yeah, anaerobic glycolysis.

01:42 They will generate ATP any way that they can, even if it's inefficient.

01:47 But that's not sufficient to maintain function.

01:50 It'll keep them alive, but they won't be functional.

01:52 So function is lost before viability.

01:56 The extent of the injury in any tissue depends on the tissue type, and the functional demand.

02:01 So remember, neurons - really sensitive.

02:05 Cardiac myocytes, pretty sensitive.

02:08 Hepatocytes, not so much.

02:11 And certainly skin and skeletal muscle, definitely not so much.

02:15 It's also going to depend on functional demands.

02:19 So a heart that is at rest, and someone who's just sitting around being a couch potato, no problem.

02:26 But if they get up and start to run a marathon, there's increasing demand, and flow may be limiting and suddenly, you can go from someone who was not having any problems at all, to having ischemia and even infarction.

02:39 And the complications that occur with infarction and ischemia are consequence of acute injury.

02:46 And then the healing process, remember the granulation tissue? All right, things for you.

02:53 I would like to challenge all of you because there are several points that we have not yet successfully attacked.

02:59 As physicians, as academicians, as people who take care of the human population, we don't know yet how to do these things and I'm hoping that you will be able to help us.

03:11 So vascular injury gives rise to atherosclerosis.

03:19 It may be impossible to completely eliminate vascular injury but, we can make atherosclerosis so much better if we just didn't recruit in those smooth muscle cells.

03:31 And those smooth muscle cells didn't make all that matrix, the wall would not be so thickened and limiting the flow.

03:39 So we might be able to reduce the amount of atherosclerosis, if we can control the way that we recruit some muscle cells, or turn them off.

03:50 We'd love to find a better way to get stable plaque.

03:53 So plaque, by itself, remember is not that bad, up to 70 percent, you have no symptoms at all.

03:57 It's when the plaque ruptures, that we have problems.

04:01 And so being able to find other drugs besides statins that will give us a thickening of the fibrous cap and a diminution of the atheromatous core, that would help a lot.

04:13 It would be wonderful if we can identify vulnerable plaques before they blow and then be able to intervene by putting in a stent or something else on the spot.

04:23 We don't yet know how to do that.

04:28 If we had better ways to keep tissue alive during injury, so if we could put in something that would allow neurons to survive beyond 5 minutes.

04:39 If we could put in something that would allow cardiac myocytes to survive beyond 30 minutes, we can actually do a lot to limit the consequences of a stroke or a myocardial infarct.

04:52 And like also, we would like to modulate the healing process.

04:55 The healing process does bring in a lot of inflammatory cells, so there's going to be a lot of secondary damage.

05:01 We'd like to maybe hasten the healing process so we don't have to have a longer period of granulation tissue.

05:08 So there are other targets that we could potentially attack when we're thinking about how to better treat our patients in the future.

05:17 And with that, I'd like to close.

05:20 Atherosclerosis is a really important topic.

05:22 It's important that we understand how it happens, why it happens, consequences of it happening, and then also, that final two slides about how we can do a better job of treating it.

05:34 Thanks.