The True Story of LDL and HDL Cholesterol
21
August

By Adem Lewis / in , , , , , , , , , , , , , , , , , , , , , , , /


Let’s go back to our dietary lipids that
have now been broken down and absorbed. Inside the enterocyte, fatty acids are re-assembled
into triglycerides, phospholipids and cholesterol esters. Short and some medium chain fatty
acids, since they are very small and more polar, can go directly into the bloodstream
where they bind to albumin, they take the portal vein and go tho the liver.
Everything else, instead, which is the vast majority of dietary lipids, has always the
same problem: lipids are insoluble in water so they cannot be sent by themselves into
the watery bloodstream. So before they leave the enterocyte, these lipids are packaged
in a particular structure which is called a lipoprotein. A lipoprotein is composed of
a core which contains all the hydrophobic lipids, and in particular triglycerides and
cholesterols, and a coat surrounding them which is composed of a layer phospholipids,
with all their polar heads facing outside, and some proteins, which are called apoproteins
and are needed for the lipoprotein to be trafficked and recognized by several receptors on the
surface of our cells. This external water-soluble shell of phospholipids and proteins, allows
the lipoprotein to float freely in the watery environment of the bloodstream or the lymph.
The major lipoprotein built in the intestinal cells is called chylomicron. The composition
of chylomicrons largely reflects the lipid composition of the food we eat, so in general
they are very rich in triglycerides, around 80 to 90%. For this reason, they tend to be
very large and have a very low density: remember that lipids are less dense than water. Because they are very large, when they exit
the enterocyte, chylomicrons do not go directly into the bloodstream, and take the lymphatic
circulation instead. They will then enter the circulation in the large subclavian vein
via the thoracic duct. The final destination of chylomicrons is the liver, however since
they don’t take the portal vein, they have a long way to go before they arrive. During
this time, the chylomicron will release most of its triglycerides to the cells of our body
that need them; mainly muscle cells for energy, and adipose cells for storage. On the walls
of the exchange capillaries with muscle and adipose tissue, is located a particular enzyme,
lipoprotein lipase, which sucks triglycerides out of the lipoproteins and brings them inside
the cells. When they arrive to the liver, chylomicrons
are still very rich in cholesterol. The liver will disassemble them, take their cholesterol
and decide what to do with it depending on what is needed. The liver may use cholesterol for its own
needs or to build bile salts, decide to get rid of it through the bile, or send it back
to the bloodstream to be used by other cells in our body. To send lipids into the circulation,
the liver builds its own kind of lipoprotein, which is called VLDL, or very low density
lipoprotein. Compared to chylomicrons, VLDLs contain less triglycerides and more cholesterol,
so they are a little bit smaller and more dense. They do not only carry exogenous cholesterol,
coming from the intestine via chylomicrons, but also endogenous, liver-made cholesterol,
since as you know the liver is able to make its own cholesterol. The main lipids carried
by VLDLs, however, are still triglycerides. Once in the bloodstream, VLDLs will give their
triglycerides to the cells via lipoprotein lipase, and become denser and relatively richer
in cholesterol. They become what it’s called a VLDL remnant, or IDL, for intermediate density
lipoprotein. VLDL remnants can go back to the liver and
be cleared from the blood, but typically, while they are still in the bloodstream, they
are converted by remodeling of their apoproteins into yet another kind of lipoprotein which
is called LDL, for low density lipoprotein. LDL is the major cholesterol transporting
lipoprotein in our bloodstream and it’s responsible for finally delivering it to the
cells that need it for growth or synthesis of hormones. Its core is mostly made of cholesterol,
which is why they are denser and smaller than VLDLs. The way LDLs deliver cholesterol to cells
is different from the way chylos and VLDLs deliver triglycerides. Chylos and VLDLs give
away some of their triglycerides via the action of lipoprotein lipase, but they stay in the
bloodstream and keep circulating. Instead, the LDL particle is completely uptaken and
disassembled inside the cell, which binds it via a specific protein on its surface called
LDL receptor. The big problem with LDLs is that if cells
don’t need their cholesterol, or if we have more LDLs in the circulation than cholesterol
is needed, then they will not be cleared from the bloodstream and will keep circulating.
A prolonged residence time of LDLs in the bloodstream makes them susceptible to structural
modifications, such as oxidation and changes in their apoprotein structures. These alterations
abolish their ability to bind the LDL-receptors and instead increase the affinity for another
non-specific type of receptor, called scavenger receptor, that is present on macrophages and
recognizes chemically modified forms of LDL. Macrophages engulfing lots of LDLs eventually
die and become foam cells, a hallmark of atherosclerosis. Oxidized LDLs are the primary cause of initiating
atherosclerotic lesions in the walls of our arteries and are strongly associated with
cardiovascular disease. A good dietary intake of antioxidants is helpful
to maintain a good antioxidant state in our bloodstream and prevent LDL oxidation. Small, dense LDLs have a much stronger atherogenic
potential because the have low affinity for the LDL receptors due to conformational changes
in their apoproteins. Consequently, they tend to stay longer in circulation, they are more
susceptible to oxidation, macrophage uptake through scavenger receptors and foam cell
formation. On top of that, smaller LDLs bind more easily to the arterial wall, and can
directly penetrate trans-endothelially. For these reasons, small dense LDLs are an independent
predictor of cardiovascular disease. It is still not clear how small, dense LDL originate.
Genetic factors clearly are important, but high blood triglycerides also play a role.
If LDLs start off containing more triglycerides, once they give them away via lipoprotein lipase,
are left with less cholesterol, and thus they are smaller and denser.
When we measure total LDL cholesterol with our blood tests, we don’t know if this cholesterol
is carried in a few, large LDLs, which is a better situation, or if it’s split in
many, small dense LDL particles, which increases cardiovascular risk. To have that information,
we must determine the number of LDL-particles, or at least estimate it measuring apoproteinB.
Since each lipoprotein particle carries only one apoprotein of the B type, the ratio of
ApoB to LDL cholesterol allows us to estimate their size. All cells can express LDL receptors, according
to their cholesterol needs. If cholesterol is in excess of a cell’s
need, then the cell will reduce the number of LDL-receptors on its surface to protect
itself from over-accumulating cholesterol. This efficient homeostatic system protects
the cell, but comes at a high price: excess cholesterol in LDLs will dangerously stay
in our bloodstream, oxidize and deposit in the walls of our arteries.
Conversely, if cells need cholesterol, they can do two things: first, they increase the
number of LDL-receptors on their surface so they can get more cholesterol from the bloodstream.
At the same time, however, they can also induce the cholesterol enzyme to start building cholesterol
by themselves. From a cardiovascular health point of view, we prefer the first option,
because it allows more LDL cholesterol to be cleared from the bloodstream.
However as we already know, a diet rich in saturated fats, trans fats and high glycemic
index foods such as simple sugars and refined grains, induces the activity of the cholesterol
enzyme and thus not only does it promote endogenous cholesterol synthesis, but it also hinders
its clearance from the bloodstream where it can do more harm. Indeed, if cells are already
making cholesterol themselves, they don’t need to get it from the bloodstream. The last important class of lipoproteins we
have to introduce is the HDL, or high density lipoproteins. These are relatively smaller
and proportionally richer in proteins, therefore they are denser than all the other lipoproteins
we have encountered. The main goal of HDLs is reverse cholesterol transport. They take
back excess cholesterol from other circulating lipoproteins and from peripheral tissues,
including dead cells and, very importantly, including macrophages and foam cells in the
arterial wall. So they take it back from them, and then, directly or indirectly, they deliver
this excess cholesterol back to the liver for elimination through the bile.
HDLs are mostly synthesized in the liver, but then they mature in the circulation by
picking up stuff from other lipoproteins and cells. Cellular cholesterol efflux and reverse cholesterol
transport is the “classical” function of HDLs, however, they have many other important
anti-atherogenic functions and in particular anti-inflammatory activity, vasodilator activity,
anti-thrombotic activity and antioxidant activity thanks to the presence of antioxidant enzymes
such as paraoxonase and glutathione-peroxidase. This is especially useful to protect circulating
LDLs from oxidation. For these reasons, cholesterol carried in
HDLs is usually labeled as “good cholesterol”, and a higher ratio between HDL and other lipoproteins
is associated with protection from cardiovascular disease.
However, not all HDL cholesterol is equally good. HDLs can become dysfunctional, pro-inflammatory
and atherogenic, especially in diabetes and other clinical conditions associated with
oxidative stress and inflammation. So while a high HDL is generally recognized as good,
this is not always the case. This is also why some important studies using
HDL raising drugs proved to be very disappointing, increasing rather than lowering cardiovascular
risk. The large, dysfunctional HDL particles generated by the drug were not efficient in
promoting cholesterol efflux and reverse cholesterol transport. So to review the functions of lipoproteins,
chylomicrons and VLDLs mainly transport and deliver triglycerides , while LDLs and HDLs
mainly transport and deliver cholesterol. Chylomicrons carry dietary lipids from the
intestine to the liver, and give away some triglycerides to cells during their itinerary.
VLDLs carry both dietary and liver-made lipids from the liver to other cells in the body.
LDLs deliver both dietary and liver-made cholesterol from the liver to other cells in the body,
but under certain conditions they may also end up depositing it in the walls of our arteries,
which is highly detrimental. Conversely, HDLs scavenge excess cholesterol from the cells
in our body, other circulating lipoproteins and the walls of our arteries, and bring it
back to the liver for disposal.


6 thoughts on “The True Story of LDL and HDL Cholesterol

  1. Awesome! just realized you had subtitles in english, that helps a lot! Love from Argentina! 😀

  2. I have watched all his videos and he is just amazing.Very clear and confident with the subject.Thankyou so much sir ! kudos to you !

  3. Hi there, have you considered Hybetez Remedy yet? Simply do a google search engine search. On there you will discover that an awesome tips about how you can cures your cholesterol naturally. Why not give it a shot? maybe it's going to work for you too.

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