From the groping in the dark to connecting genes to diseases, Linus Pauling brought the world greater clarity and visibility in biological science. He was a very intuitive character, pulling things out of the blue which were often correct. One of his conjectures was that the human collagen synthesis pathway and the lack of the most critical element to this, ascorbate (pronounce it how you will, it is always spelled ascorbate) somehow was the driving force for the majority of human atherosclerosis developed over decades in a lifetime. Rather than being a sudden, overnight phenomenon where a lump suddenly appears and you keel over from an LAD plaque burst, thrombotic, ischemic "widow maker," these bumps in the artery form over the period of years. You can even suffer a bunch of these over weeks, and they still won't kill you outright. Likewise, you don't need any unstable bumps on your arteries for a pothole in the endothelium to cause the same thrombus event by revealing a platelet sticky, damaged basement membrane.
Linus Pauling, being an expert on helical things, found that collagen, a helical thing, is the basis for healthy arteries. Old histopathology stains are not able to reveal the medial and subendothelial compartment collagens, and so for many decades, many pathologists considered collagen unimportant to arterial integrity until it was glaringly obvious in a fibrotic scar of a plaque. The Trichromes and Elastin Van Gieson stains in particular generally only detect the adventitial collagen and nothing inside. The EVG stain suggests that there is perpendicular collagen between the SMC cells, but does not mark the subendothelial collagen. Where's the collagen??? It is definitely there. The strongest collagen jacket of an artery is the adventitial layer, so when you have problems there, the artery is in deep trouble. Some dismiss the adventitia, the collagen jacket of arteries as unimportant to the etiology of atherosclerosis, but when you consider that arteries themselves are fed by arterioles entering and fed through the adventitia, the collagenous adventitia presents itself as essential to the the inner lining health of the artery. Very simply, all the collagen in an artery is important to its health. Later immunohistochemistry and EM IHC would clearly show that collagen is a critical structural element in every layer of the human artery.
Even fibrosis, which is the human body's way of filling in voids of dead and missing cells with a neutral element, rather than leave a giant hole through which massive inappropriate leaks occur, is a life perpetuating phenomenon for the artery and all organs in the body. A defective, non-functional, excess collagen patch is exceedingly more beneficial than a hemorrhage or even worse, thrombosis hole, in the mathematics of the automatic human biology. Very imperfect, but also perfect given that sometimes cells cannot divide fast enough to replace a massive loss of them.
So which one of the many collagens is so important to arterial health, and which is the intersection between Linus Pauling's vitamin C-arterial collagen-arterial health idea? Col4, which like all collagens requires vitamin C for its integrity.
Specifically, Linus Pauling cited the amounts of ascorbate that Gulono-y-lactone-oxidase carrying vertebrates are able to upregulate in times of stress that virtually never succumb from heart attacks, strokes, aneurysms, and the rest at the half point in their lifespan. In these vertebrates, it is totally unheard of for an animal at the equivalent of a human 65 years old to suffer a heart attack, even considering their massive overbearing genetic excess of HDL over LDL. Eventually, the lack of heart cell regeneration may give way to natural fibrosis and a natural lifespan end, where the heart gives out, but this is not the result of obstructive dietary cholesterol but an innate evolutionary clock.
But there must be a reason for the relative excessive ratio of LDL over HDL in the human organism. Sri Lankan elephants for example, seem to only have HDL, and are huge vertebrate mammals. It suggests that an overbearing ratio of LDL to HDL is tantamount to intellectual evolution, pointing to the criticality of cholesterol to the brain at the expense of arterial health. A true conundrum presents itself, considering that the brain needs its arteries. A very strange "what if" presents where the insulation upon axons is not cholesterol, but an artery friendly molecule. In a very vague, out of focus view, what insulation compound is mission critical to the nervous system of vertebrates is needed in a vast excess compared to its dual role in membrane and cell cycle of arterial cells. Very simply, the amount of cholesterol needed in the brain is far beyond what is needed in the artery, and important amounts of collagen are there in very specific orientations in health. If the compounds for axon health and artery health were independent, then two things could be made and this problem of one thing being helpful to one system and harmful to another system solved. A very absurd request of evolutionary processes which for humans are slow - thousands of years. We're talking about completely re-engineering the lipid genetics of humanity. In the meantime, we can pull up and pull down our levers with medicine knowing all this. Is it futile? NO. A short, perfect, benevolent life is better than a short, terrible, malevolent, life for humanity.
So if we all plan to live forever, we have to figure out how to both steel our arteries against its pot hole plaster cast, cholesterol, without starving our brains of cholesterol. It's a true conundrum.
In ending, Linus Pauling's specific recommend for large human adults was no less than 6,000 mg of vitamin C throughout a day, not in one dose but divided throughout a day to at least avoid atherosclerotic problems without other pharmaceutical interventions, specifically to enhance collagen repair within the artery. Which collagen he didn't know, but Novo Nordisk identifies this to be Collagen IV(4).
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