The Good & Bad of LDL & HDL: A Look at Cholesterol

[Monique]

Just exactly why is it that HDL (high density lipoprotein) is so good for you, but LDL (low density lipoprotein) so bad?

 

[Adrian]

From what I know about the cholesterol debate, it is actually far from clear that even LDL is bad for you; slowly people are realizing that wiping the slate clean on this one and starting all over again. The idea that cholesterol is bad traces back to the 60s and 70s, when research linked arteriosclerosis with elevated levels of blood cholesterol. People were quick to jump into conclusions and said that high levels of blood cholesterol caused arteriosclerosis, and further assumed that dietary cholesterol intake determined blood cholesterol levels.

The theory is that LDL cholesterol clogs up your arteries by forming a lining on their inside walls, and thet HDL cholesterol actually keeps LDL molecules from doing that.

Well, in fact the body produces more cholesterol precisely because arteriosclerosis has already damaged blood vessels; cholesterol helps to make them smooth and keep them from leaking ( or so the rather simplified version which I remember goes). Furthemore, dietary cholesterol intake has little effect on blood cholesterol levels. The body profuces it to suit its needs. A normal, healthy person would have to eat around 20 egg yolks a day (!) to ingest as much choleasterol as the body produces itself. Furthermore, dietary cholesterol is digested and doesn't enter the bloodstream as cholesterol.

What we basically have is 1960s/70s reserach indicating a correlation between cholestorol and arteriosclerosis, 1990s research debunking the wrong assumptions that cholesterol *causes* arteriosclerosis and depends on dieatary cholesterol intake, and a great many questions still left open.

 

[Monique]

Well, but cholesterol is different from HDL and LDL.

The reason that cholesterol is an essential molecule, is that is is an integral membrane lipid that attenuates the fluidity of our membranes, it also helps in solvating protein complexes in our membranes, which then can function as receptors or channels.

What I read on the reason HDL is good, is that it removes excess cholesterol from our vessels and that it inhibits lipoprotein oxidations (extensive oxidation causes inflammation). HDL is thus strongly protective against atherosclerosis.

I don't remember any more the structures of LDL and HDL and why the one is good and the other is bad..

 

[Monique]

Interesting, I just went through my very thick biochemistry book, I can't find a direct answer, but the structures of the molecule complexes give a clue:

Of the five lipoprotein classes, LDL is by far the richest in cholesterol, more than 40% of the weight of the LDL particle is cholesterol ester, and the total of esterified and free cholesterol amounts to well over half the total weight.

The hydrophilic layer (protein, phospholipids, etc) of LDL particles is thus much thinner than in HDL particles, and mechanical stress against the blood wall might lead them to turn inside out (I guess), causing the fatty streaks and subsequenct progression to atherosclerosis by smooth muscle cell recruitment, collagen deposition, and formation of a fibrous cap.

 

[Adrian]

Here's a nice overview on LDL's role in artherosclerosis:

http://www.lipidsonline.org/slides/slide01.cfm?tk=18

Looks like the main difference between HDL and LDL with respect to inflammatory properties is that LDL can be easily oxidized, while HDL is actually an anti-oxidant. The oxidized lipids from LDL that cause the inflammatory response can actually be reduced by HDL. Also, HDL inhibits the production of adhesion molecules on endothelial cells. Looks like several mechanisms are involved here.

 

[Monique]

Oh! Great resource website Adrian! (althought the slide load verry slow), do you know how HDL inhibits production of adhesion molecules on endothelial cells? What kind of mechanism would that be?

 

[Adrian]

Hm... enzyme inhibition? Allosteric maybe? Just guessing :)

 

[Monique]

Adhesion molecules and enzymes? I don't know about that.. you say the production is inhibited, not that the activity or reactivity is inhibited of the adhesion molecules.

For the production to be inhibited, the HDL molecules would have to enter the cell or bind to membrane receptors that relay the signal, I am not sure why HDL would do such a thing, act as a signal molecule??

 

[Monique]

This seems strange to me, why during inflammation is cell proliferation upregulated together with expression of metalloproteinases?

You are producing matrix and breaking it down at the same time right?

 

[Monique]

OK, LDL contains molecules that are easily oxidized, LDL can enter the tissue of bloodvessels, here it will attract monocytes, the monocytes differentiate into macrophages by the modified LDL.

The macrophages produce cytokines and thus attract more monocytes. The activated macrophages start engoarging the modified LDL and become foam cells. These foam cells start the inflammatory response.

HDL contains paraoxonase, which is is an antioxidant, it inhibits oxidation of LDL. HDL is able to take over the oxidized lipoproteins from LDL, which then get reduced by apo A-I and II of the HDL. HDL also causes the efflux of cholesterol from the foam cell, thus there is also the anti-inflammatory action. HDL inhibits cytokine-induced expression of adhesion molecules (by inhibiting sphingosine kinase, the phospholipid component of the HDL particle is responsible, thus on your intake of dietary fats)

GREAT! I just learned a lot :P

 

[adrenaline]

May be a little off topic but clinically we are now using a different test to look at cholesterol subfractions including Lp(a) that was not tested with routine cholesterol testing. ( In fact, the standard cholesterol test did not detect up to half the people at risk for coronary disease...many people with "normal choesterol levels" ended up having heart attacks anyway. (discounting, smoking, etc.) We now use the VAP test.

see http://www.directlabs.com/VAP.php

You see it even includes the homocystine level (independant risk factor for coronary disease), hsCRP (which may just be a general marker of the inflammatory process of coronary disease), the different subfractions of HDL and LDL (better and worse good cholesterol, and better and worse bad cholersterol!)

COMPONENTS OF THE VAP TEST include direct measured LDL, HDL, VLDL, TC with TG and LDL/HDL RATIO and TC/HDL RATIO. Additional important lipoprotein risk factors include:

Lp(a) The "heart attack" cholesterol. A direct risk factor for CAD and high levels are a predictor of stroke and post angioplasty rest enosis in many cases.

HDL2 The "best" cholesterol. Low HDL2 is a risk factor for CAD in patients with normal cholesterol.

HDL3 The least protective HDL. TC/lipid panel don't distinguish between HDL2 and HDL3

IDL "Bad" non-LDL cholesterol. Independent risk factor for CAD.

VLDL3 A predictor of the severity of CAD. The most dense (bad) element of triglyceride.

Pattern A, B or A/B "A" is the (good) atherogenic of the LDL subclasses, "B" is an independent risk factor for CAD—the most atherogenic (bad) of the HDL sub classes and "A/B" is intermediate in atherogenicity

 

[Monique]

Interesting, I am not a clinical biochemist so I don't know how cholesterol testing is routinely done? And I couldn't find how this VAP test does it and why it is better?

 

[Meninger]

Far as I know HDL serve as acceptors of cholesterol, carry it to the liver and used to synthesize bile while LDL transports cholesterol around the body for use in biosynthesis and storage.

 

[adrenaline]

Originally posted by Monique
Interesting, I am not a clinical biochemist so I don't know how cholesterol testing is routinely done? And I couldn't find how this VAP test does it and why it is better?

I believe the traditional cholesterol testing was separated by centrifugation process with separation by size and LDL was always calculated by the Friedwald equation LDL=(total chol)-(HDL)-(Triglycerides/5). However it was very inaccurate since the LDL calculation using the Friedewald equation was very inaccurate when a patient had high triglyceride levels and IDL levels .

The VAP is a direct measurement of all the subfactions so LDL can be directly measured even with triglyceride levels in the thousands. ( The procedure is very complex. Here is a detailed report by a biochemist http://www.atherotech.com/content/images/pdffiles/quantificationofcholbyvap2_1994.pdf

Hope that helps?

 

[ArnoldMathew]

Just exactly why is it that HDL (high density lipoprotein) is so good for you, but LDL (low density lipoprotein) so bad?

hello..

When too much LDL (bad) cholesterol circulates in the blood, it can slowly build up in the inner walls of the arteries that feed the heart and brain.

About one-fourth to one-third of blood cholesterol is carried by high-density lipoprotein (HDL). HDL cholesterol is known as “good” cholesterol, because high levels of HDL seem to protect against heart attack.

 

[DaveC426913]

My limited (and quite possibly wrong) understanding of the practical difference is that bad cholesterol is "sticky" and tends to collect on the walls of your arteries, leading to the expected health dangers, whereas good cholesterol is "slippery" and tends to discourage this build up.