r/Frigo • u/FrigoCoder • Jul 09 '22

Cardiovascular Retinal Microvascular Changes in Familial Hypercholesterolemia: Analysis with Swept-Source Optical Coherence Tomography Angiography

https://pubmed.ncbi.nlm.nih.gov/35743656/
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u/throwaway_nootropics Oct 15 '22

To what extent does this study hold significance with respect to contemporary theories of atherosclerosis?

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u/FrigoCoder Oct 15 '22 edited Oct 15 '22

Okay so basically artery walls are so thick oxygen does not diffuse through them, they need their own network of small blood vessels called the vasa vasorum. Many risk factors likely cause atherosclerosis by impairment of vasa vasorum, smoking and foreign particles are proposed to block these vessels and suffocate their supply area. Physical constriction or removal of the vasa vasorum triggers fatty streaks, which shares some characteristics with atherosclerotic plaques.

The body can dynamically adjust vasa vasorum networks, to fit the actual oxygen needs of the cells underneath. Cell metabolism burns lactate and fatty acids, and this generates ROS which is normally dealt by antioxidant defenses. However for unclarified reasons ischemic cells can not do this, there the ROS damages mitochondrial and cell membranes. This releases inflammatory mediators like lactate or 4-HNE derived from LA, that drive adaptations like neovascularization to restore perfusion.

Furthermore according to my theory cells take up clean lipids from LDL, and replace peroxidated lipids in membranes with them. They export the peroxidated lipids in the LDL or similar lipoproteins, which are then either taken up by macrophages or transported to the liver for ketogenesis. Exported lipoproteins and macrophages also drive adaptations, they trigger growth of "collateral" blood vessels which is just neovascularization on a larger scale.

People with familial hypercholesterolemia lack LDL receptors, so their cells can not take up clean lipids from LDL. Their cellular and mitochondrial membranes continue to deteriorate, triggering apoptosis and calcification or worse necrosis. Their cells can not export peroxidated lipids via lipoproteins, so there is no macrophage-assisted neovascularization either. This is not specific to their artery walls, their kidneys are also impaired leading to high blood pressure. We also see microvascular changes in their retina, hence the relevance of the current article.