What is Reddit's opinion of Natural History of Coronary Atherosclerosis?

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They have fatty streaks, not atherosclerosis. See this thread please https://www.reddit.com/r/ketoscience/comments/agd9k7/root_cause_for_cvd/

> 2. Natural History of Coronary Atherosclerosis by Velican and Velican -- these authors also published a series of articles in the journal Atherosclerosis covering hundreds of autopsies performed from fetuses all the way up to adults. I've been reading their papers while I await the arrival of the book. They refute several salient hypotheses in the field, one significant one being that the fatty streak is the precursor to the mature lesion. This observation is ignored to an impressive degree -- people like Attia/Dayspring citing the (apparently refuted) hypothesis that fatty streaks are precursors of mature lesions draw assumptions about the rate of progression of the disease -- e.g. when statins fail they say "obviously all cause mortality was not perturbed since the disease begins in childhood" while Velican and Velican found that a vast majority of people have no obvious fibrous lesions until their twenties. As far as I can tell the early fibrous lesion represents the first clear divergance from natural anatomical variation of the artery to compensate for things like endothelial sheer stress and fluid dynamics, but I will have to read all this in more detail. Referencing the Masai autopsies would be an interesting way to learn more here (see below).

Yeah except all endothelial and transcytosis hypotheses are bullshit because they are incompatible with observations. Lipid accumulation starts in the deepest layers of the tunica intima from the direction of the adventitia. Atherosclerosis is not uniform like glucose and lipid exposure, it more likely develops at areas of high shear stress and high vasa vasorum coverage, often leaving nearby segments and the opposite side of the wall alone. Also the most atherogenic sites have the thickest endothelial layers so transcytosis is even more questionable.

If you read Axel Haverick, Vladimir M Subbotin, possibly the Velicans, this thread, and some other works, then it becomes clear what is happening:

Diabetes and hypertension triggers endothelial and smooth muscle cell proliferation and a switch to the synthetic phenotype. Artery wall thickness grows too large for passive oxygen diffusion from the artery lumen so the deepest intimal layers start to get hypoxic. Mitochondrial ROS production triggers adaptations to hypoxia which involves angiogenesis of the vasa vasorum from the direction of the adventitia. Vasa vasorum function and growth becomes dysfunctional due to diabetes, trans fats, smoking, pollution, so it develops into a plaque instead.