PCSK9 inhibitors lower serum cholesterol by increasing the expression of LDL receptors on the liver and cells, leading to greater uptake of cholesterol from circulation.

“so the way pcsk9 inhibitor works is that it goes and tells the liver mop-up all the earlier because the LDL receptor that is there on the liver is prevented from being degraded so the LDL receptor overexpression in the liver mops up all the LDL cholesterol or the LDL lipoprotein from the circulation”

“so the pcsk9 is basically there to um to to be involved in that process and it does result in increased uptake of the ldl receptor ldl cholesterol by the ldl receptor um when you have the pcsk9 inhibitor”

“pcsk9 Inhibitors they're monoclonal antibodies and I showed a picture of this a moment ago I'll reshow it just to show you guys what's going on here on YouTube they're this little monoclonal antibody this red guy right here and it's binding the pcsk9 it's preventing it it's essentially the same thing that's happening in these people with this genetic defect in pcsk9”

“now pcsk9 is a molecule that is made by the liver and when you make more pcsk9 you're gonna um you're going to end up pulling more of that LDL out of the circulation actually you're going to leave more LDL in the circulation if you make less pcsk9 or you inhibit pcsk9 9 you're going to leave that LDL in the Circ you're going to pull more LDL out of the circulation sorry guys I keep messing it up”

“PCSK9 Inhibitors are these monoclonal antibodies which we're going to talk about in this podcast you will hear more and more about these ratha there are other ones evolocumab is ratha and they block pcsk9 this is blocking our body's ability to do this if you block pcsk9 more of these LDL receptors get pulled into the get pulled down excuse me that then the LDL receptor doesn't get recycled well it's pulling more of the LDL out of the circulation with that is the idea right”

“then the cells take up more and more cholesterol out of circulation so what basically happens is this ultimately leads to more LDL receptors being expressed at the liver and a liver takes up much more cholesterol overall so this is how the the PCS can9 Inhibitors are basically lowering serum cholesterol values by letting the liver and and cells take up a bunch more cholesterol”

“pcsk9 Inhibitors basically they are monoclonal antibodies so they're they're antibodies that block this protein called pcsk9 and what pcsk9 does is it binds to the LDL receptor and causes the degradation of the LDL receptor”

“and pcsk9 is a major determinant of how quickly you recycle your LDL receptor you do not recycle it so by putzing with the expression of that enzyme we can give you much further expression of your LDL receptor and as you said enhance clearance of your april-b particles including not only your LDL which are ninety to ninety-five percent while you're clearing remnants also”

“interestingly the ldl receptor and also the most probably important regulator of ldl receptor pcsk9 they did not pop up in uh in that g was which is uh which was a little bit uh surprising to me given the effect of of uh sk9 inhibitors on on lpa”

“so the the way pcsk9 works is that it's a regulator of the ldl receptor so when the cells makes an ldl receptor it will also make pcsk9 now pcsk9 can bind to the ldl receptor that can happen inside the cell and when that happens the ldl receptor gets degraded in the lysosome that can also happen extracellularly when the ldl receptor obviously in the hepatocyte gets stuck at the membrane but pcsk9 gets secreted so you can actually measure pcsk9 levels in the blood but when it gets secreted it can actually bind the ldl receptor and when that happens the ldl receptor cannot bind ldl particles”