0:00 In this video, we're going to talk about atherosclerosis, which is hardening of 0:13 the 0:13 arteries, actually it's in the narrowing of the arteries due to plaque 0:17 formation. 0:18 A plaque in this case is basically a waxy substance made of predominantly lip 0:24 ids. 0:24 When atherosclerosis is different to arteriosclerosis, arteriosclerosis is just 0:30 hardening of the arteries. 0:32 Now, atherosclerosis is a common cause of heart attacks. 0:36 So if here I'm drawing the heart, we have blood vessels called these coronary 0:40 arteries 0:41 that supply the heart with oxygen. 0:44 So let's take a look at two different scenarios. 0:48 Here are vessels and here are cardiac muscle cells. 0:52 Normally the blood vessels are carrying blood full of oxygen to the cardiac 0:57 muscle cells, 0:58 thus allowing the cardiac muscle cells to function normally, which means the 1:03 heart will 1:04 function normally. 1:05 However, if we look at an atherosclerosis scenario, there is a plaque formation 1:13 . 1:14 Blood can't be delivered properly to the heart or there is reduced blood flow 1:18 to the 1:19 heart. 1:20 And as a consequence, the cardiac muscle cells are deprived of oxygen. 1:26 Symptoms of atherosclerosis in the coronary arteries include vomiting, anxiety, 1:33 angina, 1:34 which is pain in the chest area, coughing and feeling faint. 1:39 So again, if the atherosclerosis in the coronary artery here is so severe it 1:44 can actually block 1:45 everything. 1:46 It can block the blood supply altogether and we get a schema of the cardiac 1:50 muscle cells. 1:51 And so as a consequence, these cells will die and you get a heart attack or 1:58 heart failure. 2:00 So atherosclerosis formation of the coronary arteries can lead to myocardial is 2:05 chemia. 2:05 But there can also be atherosclerosis formation in the carotid arteries. 2:10 This can cause symptoms such as weakness, dysphia, headache, facial numbness 2:16 and paralysis. 2:18 And this is because the carotid arteries is the blood supply to your brain. 2:21 So if you don't get any blood to your brain, you get stroke as well as these 2:26 symptoms. 2:28 Autherosclerotic plaque can cause peripheral vascular disease. 2:30 Now peripheral vascular disease is the reduced circulation of blood to a body 2:35 part other 2:35 than the brain or heart. 2:37 So for example, the liver or something else like your reproductive organs. 2:44 And this is bad in every respect. 2:47 In peripheral vascular disease, you can have hair loss, erectile dysfunction 2:51 and weakening 2:52 of the associated area. 2:55 Another important site where atherosclerosis can occur is the renal arteries. 3:00 This can cause a reduction in appetite, swelling of the hands and most 3:05 importantly, it can 3:07 trigger a renin-release which will significantly increase the blood pressure. 3:14 Okay, so there were some common sites where atherosclerotic plaques can occur. 3:20 But let's see how severe an atherosclerotic plaque can become. 3:26 So here is the increase in severity. 3:29 The first blood vessel here is normal with normal blood flow as we can see. 3:34 A plaque can form within the layer of the blood vessel. 3:38 Firstly it will be growing downwards, so pushing the vessel down. 3:45 When more plaque forms, the plaque begins growing upwards so it will actually 3:50 narrow the blood 3:51 vessel. 3:52 If the plaque keeps growing, severity increases and the blood vessel really 3:57 begins to narrow. 3:58 The massive plaque, at the end, can actually then rupture, forming a thrombus, 4:03 forming 4:04 a clot, which will stop or impede blood flow. 4:09 When an atherosclerotic plaque ruptures, it is serious. 4:15 Now that we get the overall picture, let's look at the mechanism of plaque 4:20 formation in 4:20 a bit more detail. 4:23 So let us zoom first into this blood vessel and look at its different layers 4:28 and what 4:29 they contain. 4:33 So here is our endothelial cells. 4:38 And here is the lumen where we have red blood cells and also lipoproteins, such 4:43 as LDLs, 4:44 which are low density lipoproteins. 4:49 Surrounding the endothelium, we have the tunica intima and then the tunica 4:56 media. 4:57 In the tunica media, we have smooth muscle cells that are important in 5:01 contraction of 5:02 vessels. 5:04 Surrounding the media, we have the adventitia, which is essentially a connect 5:10 ive tissue. 5:11 There are a few theories of how atherosclerosis begins. 5:16 One theory suggests that there is endothelial dysfunction and when there is 5:23 high amounts 5:24 of circulating LDLs. 5:28 Because there are high concentrations or high circulating low density lipoprote 5:33 ins, low 5:34 LDLs, these LDLs can deposit in the tunica intima and then become oxidized. 5:42 Most LDL activates endothelial cells, causing the endothelial cells to express 5:50 receptors 5:51 for white blood cells on their surface. 5:55 So to summarize here, I wrote increase in LDLs, deposits in tunica intima and 6:00 becomes oxidized, 6:01 which will activate endothelial cells. 6:13 So here I am drawing the same layers of the blood vessel and we can see there 6:17 is accumulation 6:20 of oxidized LDLs, which will activate endothelial cells, which will begin 6:27 expressing adhesion 6:29 molecules for white blood cells. 6:33 Adhesion of white blood cells, adhesion of blood leukocytes to activated endot 6:33 helial cells 6:41 will allow monocytes and to help their cells to move into the tunica intima 6:48 layer of the 6:49 blood vessel. 6:51 When monocytes move into the tunica intima, they will become macrophages and 6:57 macrophages 6:58 will then take up these oxidized LDLs and then become foam cells. 7:06 The foam cells are key in atherosclerosis. 7:11 Foam cells do many things. 7:14 One of which is it promotes migration of smooth muscle cells, SMC, from the tun 7:21 ica media into 7:22 the tunica intima and also promotes smooth muscle cell proliferation. 7:34 An increase in smooth muscle cell proliferation heightens or increases 7:39 synthesis of collagen, 7:40 which can lead to hardening of the atherosclerosis plaque. 7:47 During this whole process, foam cells will also die, releasing its lipid 7:52 content. 7:53 This drives the growth of the plaque. 7:57 As the plaque grows, it builds in pressure, which can cause rupturing of the 8:02 plaque itself, 8:03 which is where things can become serious. 8:08 Here again, we have the tunica intima and tunica media of the blood vessel. 8:12 Here are the smooth muscle cells which have accumulated in the tunica intima 8:18 layer as 8:19 well as collagen. 8:21 Foam cells are here and they die together with other cells in the area. 8:26 Here we have dead foam cells with lipid content spilt out. 8:30 The growth of the plaque is this area here. 8:35 Now the plaque can then rupture, which can lead to thrombosis. 8:39 Thrombosis is when the plaque ruptures and where coagulation happens to stop 8:46 the plaque 8:47 from spilling its content into the lumen. 8:51 This forms a thrombus, a clot, which can impede blood flow and cause serious 9:00 complications. 9:03 That was a bit of detail of how atherosclerotic plaque forms and how it rupt 9:09 ures, but let 9:09 us go a step further and look at it in a bit more detail and a better diagram 9:17 maybe. 9:18 Here we have the endothelial cell, the tunica intima layer and the tunica media 9:23 layer containing 9:24 smooth muscle cells. 9:27 Here is our lumen, the inside of the blood vessel where we can find red blood 9:32 cells and 9:33 we can find circulating low density lipoproteins. 9:37 This black dot here of the LDL is called the protein part. 9:44 Anyway, let us just say we have a dysfunctional endothelial cells. 9:51 This allows a lot of LDLs to basically move into the tunica intima layer. 9:58 When it moves into tunica intima layer, the dysfunctional endothelial cells 10:03 release reactive 10:04 oxygen species and other enzymes such as metalloproteases, which will oxidize 10:11 the LDL. 10:12 When the LDL is oxidized, it cannot actually leave the tunica intima, it's 10:18 trapped. 10:19 Okay, the dysfunctional endothelial and the subsequently oxidized LDL triggers 10:27 the endothelial 10:28 cells to remember express adhesion molecules for white blood cells. 10:34 So here we have a monocyte circulating around, it attaches to these receptors 10:38 and then it 10:39 will move in. 10:40 When it moves into the tunica intima, when monocytes move into tissues, they 10:44 become macrophages. 10:46 So here we have a macrophage, three. 10:49 The macrophage has a receptor, a scavenger receptor that will basically eat up 10:55 or that 10:56 will take in this oxidized LDL. 10:59 The macrophage engulfs this oxidized LDL and then it will become a foam cell. 11:05 Now foam cells, they are basically macrophages containing lipids and they have 11:09 many, many 11:09 functions. 11:12 One of which is that it will release chemokines to attract more macrophages. 11:20 Foam cells can also do, step four here I'm drawing, it can release IGF-1, which 11:27 is basically 11:27 a growth factor and this growth factor will cause smooth muscle cells to 11:33 migrate and 11:34 cause smooth muscle cell proliferation in the tunica intima. 11:39 So here we have the smooth muscle cells in the tunica media layer and they will 11:45 migrate 11:46 into the tunica intima layer and they will proliferate. 11:51 And here because we have a lot of smooth muscle cells, step five, they make 11:57 more collagen. 11:58 Foam cells in step six can also die and they will die, releasing their lipid 12:03 contents, 12:04 including DNA materials. 12:07 This DNA material will actually attract neutrophils because it's sort of, it's 12:11 actually inflammatory 12:12 in this respect. 12:15 Foam cells can also release pro-inflammatory cytokines and reactive oxygen 12:22 species and 12:23 this together with neutrophils will increase inflammation in the area and this 12:29 area is 12:29 actually now the plaque because it's got foam cells, it's got dead, dead foam 12:35 cells, 12:35 it's got collagen, it's got smooth muscle cells, it's got all this stuff and 12:39 this makes 12:40 up the plaque. 12:48 Another interesting thing that occurs is there is an increase in blood supply 12:53 to the 12:54 layer of the tunica intima, to the vessel. 12:57 So it's, if you didn't know, blood vessels have its own vessel supply. 13:03 And these vessels are known as vase of xorum. 13:08 Anyways, these T cells also have a role in atherosclerosis. 13:15 So these T cells, they can bind onto adhesion receptors which are expressed on 13:19 endothelial 13:20 cells. 13:21 They then enter the area, they enter the plaque area, they can be activated by 13:25 macrophages 13:26 and they can begin releasing other substances such as interferon gamma, inter 13:31 feron gamma 13:32 essentially promotes inflammation and it activates endothelial cells to attract 13:37 more 13:37 wide blood cells and everything else. 13:39 So this plaque essentially will just keep growing, it will cause, it causes 13:45 foam cells 13:45 to die, it's, there's increase in lipid content, there's inflammation and then 13:51 all this as 13:52 it grows it can rupture and this is when thrombosis occurs, rupturing. 13:58 And when it ruptures, a thrombus can form, a clot can form and a clot forms 14:03 when there's 14:04 heaps of platelets, heaps of clotting factors that all aggregate to the area 14:09 and all this 14:10 can impede blood flow. 14:14 So that was a video on atherosclerosis, I hope you enjoyed it, thank you. 14:22 [BLANK_AUDIO]
