Gene therapy to lower cholesterol

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This week we will talk about cholesterol, the molecule that causes so much damage in the population, and how gene therapy, the use of genes as a therapeutic tool, may be the great solution that we were all waiting to face …
First of all, it should be noted that cholesterol is an essential component for our organism since it is part of cell membranes and is necessary for the synthesis of hormones and bile salts, involved in digestion. That is why our cells are able to synthesize it in the event that the diet is not able to supply cholesterol to all the cells that need it.

And although it is ingested in the form of cholesterol, it is immediately transformed into cholesterol ester, which is nothing more than the combination of the cholesterol molecule with one or more fatty acids. In addition, to be transported by the blood, they need to be combined with proteins called lipoproteins, a combination of fats and proteins.

Having clarified these concepts, we will begin to understand how cholesterol moves in our body. When we eat a food rich in cholesterol, a fried egg or a little bacon, after having undergone the digestion process, the remains of these foods reach the intestine, where the absorption of nutrients occurs. It is the cells of the intestine that produce lipoproteins called chylomicrons.

These chylomicrons act as transporters of cholesterol esters, taking them, through the blood, from the intestine to the fatty and muscular tissue, where they will leave the fatty acids and will only keep the cholesterol that will eventually reach the liver. In this organ, it will be used for the formation of bile salts and their transformation into other molecules.

At this point, other proteins, the VLDL, are in charge of transporting, in the form of esters, all the cholesterol in the diet that has not been used by the liver. Like chylomicrons, VLDLs release fatty acids as they pass through adipose and muscle tissues. It is then when cholesterol begins to be transported by LDL, which will take it to all the tissues of the body.

When LDL reaches the cells that make up these tissues, they must be recognized by receptors that will be in charge of allowing cholesterol to enter or reject it.

What happens if these cells already have enough cholesterol? Three things: Endogenous cholesterol synthesis is stopped, intracellular stores of cholesterol are created and finally, the entry of cholesterol that comes from LDL is closed, eliminating the receptors that recognize them. This is how LDL accumulates in blood, returns to the liver and starts all over again.

What does our body do to try to compensate for this excess? Use other lipoproteins, HDL to remove cholesterol from the tissues and thus facilitate the entry of more LDL, lowering its concentration in blood.

If the intake of cholesterol in the diet is normal, this whole mechanism will work in a balanced way and in the end there will be no accumulation of LDL. What if the cholesterol intake is excessive? LDL accumulates in the blood since there is excess cholesterol that the body does not need and that HDL is not able to eliminate.

What do they do in blood? They are deposited on the outside of the arteries causing the famous atheroma plaques that, apart from blocking the blood supply, can fragment, generate a thrombus and produce ischemia or embolism.

Is this process inevitable? Of course not! This only happens if the cholesterol intake in the diet is higher than our needs. If we control the diet and ingest the adequate cholesterol, the cell balance will be correct, everything we ingest will be consumed and there will be no circulating LDL causing the formation of these plaques.

What is the current solution to treat high blood cholesterol?
Drugs that are based on reducing endogenous cholesterol synthesis, such as the famous statins, and drugs that try to reduce circulating LDL levels. In addition, you can block the entry of cholesterol from the diet with the famous Danacol-type drinks, rich in plant sterols, and of which we discussed in another POST.

However, the most recent method targets the PCSK9 protein. This protein accompanies LDL from the blood into the cells of the body tissues. In order for these LDLs to enter our cells, they must be recognized by receptors that we have previously mentioned.

When there is interaction between receptor and LDL, a vesicle is formed that introduces both the receptor and LDL into the cell, as well as the PCSK9 that accompanies them. It is then that this protein destroys many

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