High shear stress. wait wait wait, no. Low shear stress. Wait wait. Low then high shear stress. Oh, okay high shear stress too.

The problem is that you don't have high shear stress WITHOUT high tensile strain, all while disregarding oscillatory tensile strain, pulsatile acceleration between peak systole and diastole, as well as vortice formation.

In my own opinion after carefully digesting all viewpoints, it seems that tensile stress and vortice formation are the most important damaging forces upon an artery.  Shear stress is most contradictory if you disregard vortical turbulence/stagnation, and once again, tensile strain.

Shear stress is basically "drag."  Like a hand in the wind palm forward, the drag on it is higher than when the hand is held parallel to the wind, creating less drag.  How high drag is better for the artery than low drag is explained by the high drag drawing the endothelium tight, like a comb over a dogs' fur in a straight, undeviating stroke.  Low drag is supposedly bad for an artery because it doesn't pull the cells tight.  To me that doesn't make a lot of sense, but when pulsatile flow (a slight backwards flow on diastole with a majority forward flow on systole) is taken account, that makes sense.  Also, vortical formation, is important, but these things are never mentioned in one sentence, causing major confusion.  It is not that hard to understand together, it makes it more confusing and ambiguous not to talk about all these things at once.  Low shear stress + pulsatile flow caused by a local pressure differential + vortices (tornados of the blood) cause the endothelium to become dissheveled.  Like taking your hand and making random circles in your pet's fur, this will cause the once linearly oriented cells to become haphazardly arranged rather than in the direction of the laminar flow.

It is counterintuitive.  LOW SHEAR STRESS causes atherosclerosis not high shear stress.  Studies in coronary arteries show a precise opposition between high shear areas free of plaque and the low shear area laden with plaque.  The problem most have is to confuse shear stress with tensile stress (combined radial, circumferential, longitudinal).  Like the thumb and the toe, they are absolutely different things.  But more confusing, when there is a big plaque, there is high shear stress in the throat it makes with lumenal occlusion. Then, high shear stress may rip open the plaque, causing thrombosis and downstream ischemia.  All the while, tensile stress is proportional to shear stress, and higher tensile stress causes more load on the force bearing elements of the arterial ECM, which invariably only causes one thing:  wear and tear (literally).

With venous systolic pressure up to ten times lower than arterial systolic pressure, it is not difficult to understand why arteries always endure more tensile strain.  Whatever the shear stress condition, tensile strain in the artery is always higher than in a vein, partially explaining why only thrombosis is found in veins but no plaque.  It is interesting to note that a vein placed in the coronary bed for bypass does then suffer plaque stenosis when it never did before.  What is the sudden difference?  Systolic pressure and tensile strain is much higher in the arterial bed.

Yet there are instances when high shear stress contributes to arterial damage, such as a biscupid aortic valve.

You'll see above, that the high shear stress area (which is invariably a zone of high tensile strain) coincides perfectly with proximal aortic dissection, the Stanford Type A, Debakey Type II dissection, as well as a frequent site of aortic root (not sinus) plaques.

Valve-Related Hemodynamics Mediate Human Bicuspid Aortopathy

Superb Blog of Blog: "Ancient Transporters: HDL and LDL Lipoproteins Carry Precious Cargo "

This is a scientific island of common sense worth visiting.  Extremely insightful and ties together things far apart for an understanding with "range."

http://drbganimalpharm.blogspot.com/2013/03/ancient-transporters-hdl-and-ldl.html

Bathe your insides with green plant juice.

Why would you do that???

TNF-alpha shreds your arteries and causes plaque to start forming

Chlorophyll prevents TNF-a from doing its business to you.

Therefore, green plant juice may prevent atherosclerosis.

Cholesterol does not cause atherosclerosis. Oxidized cholesterol byproducts do.

Here are a few things to keep in mind:  1) Cholesterol is not soluble in water or blood.  A derivative of cholesterol that is soluble in blood or water is not cholesterol.  2) The only way cholesterol is moved around either in the blood or as an adduct is by the action of adding a hydrophilic protein or converting free cholesterol enzymatically to a soluble form.  3) The only way cholesterol gets to an artery wall is through a lipoprotein or the soluble form made first by a cell's action upon ingested cholesterol.  4) It has already been proven that native LDL is harmless to endothelial layers even in very high concentrations of the particle and that the oxLDL particle is the one that causes havoc to the endothelial layer.

That being said, even in the most severely diseased coronary artery disease (CAD) patient with acute coronary syndrome (ACS) presenting as angina, respiratory problems, and/or MI, the level of oxLDL is 4-5mg/dL maximally.  Normally, they are half this value to none.  This value of 4-5 doesn't occur until after the coronary artery disease, so how could it be that oxLDL caused the CAD?  Temporally, and logically, oxLDL could not have caused CAD if it was absent beforehand.

There is no question that toxic adducts of cholesterol DO cause arteriosclerosis and the consequence is atherosclerosis.  Is it an inevitable event that cholesterol becomes 25-hydroxycholesterol and cholestane-3beta, 5alpha, 6beta-triol, the culprits of endothelial aggravation?  No.

It is not cholesterol, it is OXIDATION that causes these culprit oxidized cholesterol molecules to arise and cause harm.  By having administered pure non-oxidized cholesterol to the artery cells with no harm, scientists made sure of the fact as early as 1976.  Extending the first post, here are younger studies confirming the first.

Effect of auto-oxidation products from cholesterol on aortic smooth muscle cells: an in vitro study.

Cytotoxicity of oxidation derivatives of cholesterol on cultured aortic smooth muscle cells and their effect on cholesterol biosynthesis.

Ironically, the hydroxycholesterol and other oxygen adducts shut off cellular cholesterol synthesis, making the matter worse as your cells, especially the fastest dividing ones, make it for a mission critical reason.  As the repeat, "Purified cholesterol showed no cytotoxic effect and minimal inhibition of cholesterol biosynthesis"

Inhibitory effect of cholesterol oxides on low density lipoprotein receptor gene expression.

Again, after two decades, the groups repeat that ". Pure cholesterol showed only minimal inhibition."

The question of importance is how much of the toxic oxygenated cholesterol is there in food?  Who would know for something boiling around in hot oil and open air for weeks?  My guess is a significant amount of cholesterol has turned to ox-cholesterol and probably stuff like that should be avoided.  Minimally cooked foods, or fresh foods would have a minimum of this toxic cholesterol derivative.  So indeed, the way meat is cooked may be a significant way to introduce these cholesterol-oxygen problem compounds in the blood, and these are indeed soluble.
 
However, like most everything, there is a reason for this artery aggravating 25-hydroxycholesterol (immune response against viruses) to exist:

Armand-Frappier Outstanding Student Award--The emerging role of 25-hydroxycholesterol in innate immunity.

25-Hydroxycholesterols in innate and adaptive immunity.

There is an enzyme that responds to interferon by hydroxylating cholesterol.  25HC is antiviral.

Given that your blood levels of ApoB bound cholesterol are from your liver and not from a vat of oil boiling around for weeks, it would not cause any arterial injury.  This is dependent on antioxidant functions preventing oxidation.  These are enzymatic, such as PON and glutathione, and enteral/parenteral such as Vitamin C, E, and A.  

Pure cholesterol versus oxidized cholesterol and the role of antioxidants.

Now this is interesting.  "Purified cholesterol at the same dose produced no effect."  This painstaking chemistry is rare and goes to show that you can call something cholesterol, but it may not actually be cholesterol.  All these oxygen adducts of cholesterol and other junk are very aggravating to the artery, causing "intimal, fibrous lesions without foam cells or hypercholesterolemia" the sort of thing you might see in advanced scorbutic lesions of the artery wall.  This probably pertains to cheap Vitamin C too, which might contain some harmful junk.  Pure Vitamin C of good quality, not questionable and impure, is probably as important.    

Arch Pathol Lab Med. 1976 Nov;100(11):565-72. Angiotoxicity and arteriosclerosis due to contaminants of USP-grade cholesterol. Imai H, Werthessen NT, Taylor CB, Lee KT. Abstract Impurities were concentrated from several lots of cholesterol by recrystallizing cholesterol from methanol solution, retaining the mother liquor, and evaporating the residuum to dryness under vacuum. This concentrate contained the products of spontaneous oxidation of cholesterol and other contaminants from the original source. The concentrate increased the frequency of dead aortic smooth muscle cells and induced focal intimal edema in the rabbit 24 hours after gavage at 250 mg/kg. New or old cholesterol was similarly angiotoxic, the old more so than the new. Cholesterol purified via dibromination induced an increase in aggregate debris in 24 hours at 250 mg/kg but no increase in degenerated cells. The concentrate administered at a total dose of 1 gm/kg/seven weeks induced intimal, fibrous lesions without foam cells or hypercholesterolemia. Purified cholesterol at the same dose produced no effect.

The problem with food is that unless you keep it under nitrogen and don't cook any of your food, invariably there will be some oxidized cholesterol products.  My arteries balk at the sight of this crud.  The good news is that unlike the experimental condition above and in other experiments adding oxidized cholesterol, there isn't a whole lot of it in what you eat unless you exclusively eat low quality fast food that is fried the hell out of in oil that recirculates and boils in the air for sometimes weeks at a time, which is like an oxidation factory.  Then you might worry some about oxidized cholesterol.

The good news is that there is an enzyme that can prevent LDL oxidation called paraoxonase.

Paraoxonase active site required for protection against LDL oxidation involves its free sulfhydryl group and is different from that required for its arylesterase/paraoxonase activities: selective action of human paraoxonase allozymes Q and R.

The reality is that cardiovascular disease is rampant in industrialized nations where there is plenty of fruits and vegetables available 365 days a year.  If apples and oranges were the cure for heart disease, there would be no heart disease in the US.  By logical deduction, it is not a lack of orange or apple, but something else.

Like a broken record, many scientists the world over have implicated that the human need for Vitamin C and other essential nutrients is much greater than what the RDA maintains, and unfortunately what food can deliver.  Unless we all start eating a whole bunch of acerola cherries all the time, for example, you would need to eat 30 oranges a day or drink the equivalent of fresh squeezed juice to get a modest 2.7 grams of ascorbate.  The whole point of the idea of vitamins was to cover what nutritious food, like oranges and apples could not provide, especially given that trees only fruit 3-5 months a year, leaving humans ravaged by scurvy during the non-fruiting season, therefore creating the situation "cyclical scurvy."  When Vitamin C containing fruits and vegetables are available in the growing season again, the atherosclerosis accelerates during this period, not reduces, in order to build a more scurvy resistant arterial wall.  You want to have a consistent optimal dose at all times.

Now that was a tangent, but not really, as serum antioxidants like Vitamin C have everything to do with preventing cholesterol oxidation and enhancing PON function.  The understated and amazing observation made in 1976 is that purified cholesterol, free of oxidation products and contaminants, is harmless to the artery wall. 

Atherosclerosis Is Not A Modern Disease. Lifespan Was Shorter Not Longer In Ancient Humans.

Looking at atherosclerotic plaque in people 4000 years ago.

Today we are awash with paleo diet recommendations or vegetarian/granarian/fruitarian diets, all consumed by ancient human beings.  They DIDN'T live longer, they lived much shorter lives.  People never reached 50 years of age, and this age was correlated with rampant atherosclerosis (plaque).  They certainly had orange and apple trees back then.  There is no shortage of apples in Europe, so that is clearly not the cause of atherosclerosis in Europe.  It is not because of an "apple tree deficiency."  Our clean eating ancestors had severe atherosclerosis before the age of 40.  Why could this be?  They ate plenty of apples...

The German and Norse Pagan festivals featured many many apples (to eat). "Brita as Iduna" (1901) by Carl Larsson:

We have a heritable in-born genetic defect of ascorbate synthesis that goes beyond just a sprinkle or dash.  It was the great pioneers such as Pauling, Stone, Cameron, Willis, who initiated the idea of megadose ascorbate consumption (which is not mega but actually normal).  The schizophrenic contradiction of wanting this threshold rescue dose of this genetic defect to be lower by the day is pure insanity.  It is like saying one day humans will not need to drink several glasses of water a day to be alive.  It "ain't gonna happen."  The orange tree idea takes us to square one, as the therapeutic dose for atherosclerosis is minimally 4,000 mg ascorbate.  That is 40 oranges, more than a tree may make all year.   Until the day we as a species actually genetically engineer back a working copy (is this natural?) to replace our corrupted yet present Gulo gene, we will need to take in effective amounts of the rescue substance, ascorbate.

That is the whole idea behind science, the mastery of our biological weaknesses, and so called "vitamins."  If we are naturalists to the extreme, throw away your computer, wear burlap sacks, live like a Quaker and we can forget about vitamin pills altogether, plunging ourselves all the way back to 4000 years ago where people were rife with atherosclerosis and lived to a little over 40 years of age despite "perfect" natural diets with no fried or packaged foods.

It's the missing substances, stupid.

Lipoprotein(a) and macrophages in tandem within a human coronary plaque biopsy:

Here are some pictures of Lp(a) together with macrophages taken from a human coronary atherosclerotic plaque.  Panel C are the macrophage foam cells, Panel D is Lp(a).  They are clearly one on top of the other.

This is taken from: Lipoprotein(a) and inflammation in human coronary atheroma: association with the severity of clinical presentation  from all the way back in 1998.  It would be inaccurate to say that there is only 1 person on the planet who recognizes Lp(a) as an atherogenic factor.

The question of causality and time-frame is always to question.  The essential point we're trying to make is that Lp(a) doesn't just swoop in from out of nowhere for no reason all the sudden.  Macrophages which do home into inflammatory cytokine signals emitted by the artery, and do burrow in to receive cholesterol via active receptor exchange to return to the liver, also don't just suddenly go in and start chewing up lipoproteins.  That being said, foam cells and Lp(a) happen together frequently.  In any remodeling process in the body, there is nearly certainly found macrophages.  You can't just ignore the immune system.

What is my position?  It is irrelevant.  It is beyond irrelevant "who is right," but what is germaine is "WHAT is right."  I do not care "who" is right, nor should you.  Those who care intensely about who should be right obviously have something else driving them like a jerk's ego or some frivolous vendetta.  The question should be, how do we make each and every one of the millions of people of Earth right in their application of science.  What we should all care about is "what is right," not "who is right."  Needless to say, that is my concern in science, no extraneous nonsense.

What is true is that macrophages are initially participating in a beneficial remodeling process, and not chewing up ox-LDL in some parasitic process, but attempting to hand back the remodeling waste, the construction site debris back to the liver for recycling via....HDL.  We certainly can't ignore HDL in this repair process either.  It will spin cardiopathology's noodle when they see that the majority of atherosclerotic plaques are rich in ApoE, which if extended the old logic applied to LDL is causing harmful things.  On the contrary, the presence of ApoE we all know to be part of the repair process which may be overwhelmed by a net excess of damage as opposed to a net excess of repair.

Does Lp(a) cause atherosclerosis?  Only if there is a reason for atherosclerosis to take place.  For a many humans who eat just an orange a day but still have the Gulo-/- genetic defect, there is a lot of cumulative damage that does occur which needs patching by Lp(a) and the coagulation system.  Think of it this way, when thinking about preserving arterial integrity: a normal rat makes the equivalent of 5 grams a day in a 70 kilo human when nothing is going on.  In stressful times, a rat makes 300% more vitamin C.  This entry certainly is not encouraging or supporting the fallacy that dietary cholesterol causes heart disease.  It does not, but other dietary factors such as too low vitamin C, B, E, magnesium, K, D, amino acids and too much trans-fatty acids and omega-6 do.  The recent US Federal guidance to stop paying attention to ingested cholesterol is a well-studied one made with decades of clinical evidence that cholesterol consumption has historically had nothing to do with the rate of heart disease.

I think this statement I made a long time ago sums it up nicely about what is going on:

 "A big lump is better than a big hole."

One prevents lethal hemorrhage, the most dramatic example in human biology being the aortic dissection with adventitial failure, the other is lethal hemorrhage.  One of the first priorities of the human physiology is to stop bleeding and hemorrhaging.  It drops everything it is doing and attends to that first, even if it means making a pile of disorganized stuff at the site of leaking that is harmful down the road.  Better than bleeding to death.  Lp(a) is very atherogenic at sites of arterial damage, and sticks more to the glycocalyx with ascending concentrations.  If the endothelium is in tact, there is nothing for Lp(a) to react to, no ligand, no binding site to the ligand.  Lp(a) just floats along harmlessly as it does not encounter plasminogen binding sites, free lysyls, fibrin, exposed subendothelial fibronectin, etc.  You can't just ignore the coagulation system either.  Lp(a) has a direct affinity to fibrin(ogen) which is Clotting Factor 1, and gets cross-linked to fibrin clots via FactorXIII.  Do macrophages foam cells CAUSE atherosclerosis?  No.  They are attempting to prevent it, but the process can and does go wrong if they get overwhelmed.  When they are participating in arterial repair, foam cells are formally defined as early plaques, but that is simply a matter of scientific semantics.  Perhaps one day, they will be relabeled as "reparative cells" distinct from a fibrofatty mass devoid of cells that can rupture and cause thrombosis. Given an equal sized foam cell lesion and fibrofatty mass with thin cap that is  less than 20% occlusive, the unstable fibrofatty mass is the dangerous thing, and the foam cell lesion is unconcerning.

Macrophages and foam cells are not always in human atherosclerotic plaques.  In fact, many times, they are not there at all.  Many pathologist specimens of human diseased atherosclerotic arteries do not have foam cells, which is why some scientists choose to de-emphasize them or diminish their importance.  But they do happen, and we can't just ignore them.  One improvement in the future state-of-the-art may be to put macrophages and foam cell "lesions" in a category all on their own as they are dynamically different from all other component atherosclerotic plaques, and not just different in cellular origin and composition.  They also serve an entirely different purpose altogether than other cells found in human plaques, including remodeling, debris clearance, and returning the artery back to its original state.