Functions of the Endothelium

00:01 Under Part 2 here then.

00:02 Let's talk about the endothelium.

00:04 And again, I will say and I will repeat over and over again, it is not just the lining of blood vessels.

00:10 It's actually a very important cell type that regulates a lot of things in the circulation.

00:18 Back to our artery and vein, so we have endothelium centrally associated with the intima.

00:25 It lines the blood vessels, we have to have an intact endothelium otherwise, we will have problems with thrombosis and blood clots.

00:35 Okay, so what does the endothelium do and again, all the little details on the right hand side, don't get too bogged down.

00:42 If you want to see what that is all about.

00:45 There is a separate talk on coagulation that I did in one other part of the Lecturio lectures, so don't sweat that too much.

00:52 The main take home here is that bullet on the left.

00:56 Endothelium maintains blood in a fluid state, so it regulates coagulation, and it makes a number of factors that makes that possible.

01:06 It makes a number of factors that locally regulate smooth muscle tone, we've talked about nervous innervation that regulates smooth muscle tone in the arteries, whether they're relaxed or contracted.

01:19 But there are things that are made locally by endothelial cells that also affect the underlying smooth muscle cells of the media.

01:27 So nitric oxide and prostaglandin I2 or prostacyclin, that's the other name for it are vasorelaxants.

01:36 Vasoconstrictors include angiotensin II that is made as a result of the endothelium acting on angiotensin, to make the the final peptide that's active.

01:49 Endothelial cells make endothelin.

01:52 They are going to be involved with platelets that are going to be making thromboxane A2 and superoxide anion, the O2- is also going to be a very potent vasoconstrictor.

02:09 Okay.

02:13 As already indicated, endothelial cells are important for metabolizing a variety of hormones.

02:19 So again, all the details on the right hand side we'll cover in a separate talk, don't get too bogged down on this, except to see that angiotensinogen that has been acted on by renin released by the kidney, when it says, "We don't have enough blood pressure dudes, we need to increase our blood pressure".

02:36 Renin acts on that precursor angiotensinogen to angiotensin I.

02:42 And then there's a converting enzyme made by endothelial cells, that converts that to the active ingredient, the angiotensin II that acts on a receptor to cause vasoconstriction.

02:55 Endothelial cells are really important for regulating inflammation.

02:59 At those postcapillary venules, the endothelium interacts with neutrophils, mononuclear cells, such as lymphocytes, and monocytes to bring them into sites of inflammation.

03:13 So it is a very delicate dance that is performed between the inflammatory cells and the endothelium.

03:20 This is just showing you more of that schematic.

03:23 Again, this was a separate talk in other places in the Lecturio lexicon, so you can look this up in greater detail.

03:31 But basically leukocytes are coming along.

03:33 And they don't just kind of happen to glom onto endothelial cells.

03:38 There are in fact a number of molecules, such as E-selectin and P-selectin that bind to glycoproteins on the inflammatory cells that allow them to roll and then the endothelial cells make integrin ligands.

03:55 They're going to be the integrin super family of ligands such as intercellular adhesion molecule-1 that will allow the binding to integrins that have been activated on the surface of the inflammatory cells.

04:10 And you see that highlighted there.

04:13 And then, within the inflammatory cells crawl across the endothelium that involves a interaction with various molecules such as PECAM, platelet endothelial cell adhesion molecule, otherwise known as CD31.

04:30 At CD31 on the endothelial cells interacts with CD31 on the inflammatory cells allowing them to crawl across.

04:38 So you can see inflammatory cell recruitment very definitely.

04:43 An integrally involves the interaction of endothelial cells and inflammation.

04:50 Endothelial cells have to transport fluids, metabolites and larger molecules.

04:56 On the right hand side, you can see that from left to right, you can see that there's diffusion, there's paracellular transport, there's carrier-mediated transport, there's receptor-mediated transcytosis, there's absorptive transcytosis, there is active efflux.

05:12 So there are a variety of ways that things can get from one side of the endothelium, which is where the fluid is where all those metabolites are back out.

05:21 And conversely, things that are being synthesized or metabolized, or waste products in the extravascular space have to be transported back out into the circulation to be taken someplace else.

05:34 What's being shown here is actually the interaction between endothelium and astrocytes within the blood brain barrier, which is a relatively tight barrier.

05:43 And yet, we have to transport a whole bunch of stuff.

05:47 So at the brain can function that's a very highly metabolically active tissue.

05:52 And as we already talked about, endothelial cells will also influence smooth muscle cell growth, and in fact, it's a major mediator.

06:01 Endothelial cells, major mediator of the process that's going to be atherosclerosis.

06:06 And again, there are lots and lots of details, I refer you to another talk that I've done elsewhere, talking about how atherosclerosis occurs.

06:16 Endothelial cells are the source of new endothelial cells.

06:19 So if we've had damage and we have to have neovascularization, angiogenesis that has to come from existing endothelial cells, so they have to be able to be kicked into the cell cycle and have to grow, proliferate, migrate and formed new tubes.

06:36 So these guys are really much more than just lining cells.

06:42 Okay.

06:43 I think I've beaten that course very effectively.