Summary about Atherosclerosis     Unsolved Problems    Dec. 1, 2017

Atherosclerotic blockage and weakening of arteries kills more people than any other disease, including cancer. Disturbing blood supply to the brain results in strokes; blocking flow through arteries of the heart results in heart attacks; and irreversible damage to kidneys is a third major cause of deaths resulting from atherosclerosis. All three of these typically reach advanced stages before symptoms are detected. Methods can detect blockages, however.

The material that blocks arteries is called "plaque" but is not a particular substance.
Popular magazines and newspapers tend to leave one with the false impression that atherosclerotic plaque consists of thimble-sized, non-living, blobs of cholesterol mixed with trans-fats, suspended in the blood and bouncing around inside blood vessels.

Those are misguided ideas. For one thing, "plaque" is never located inside the lumen of any blood vessel (i.e. not in the area where blood flows). Instead, "plaque" forms in between the smooth muscle cells of the artery walls themselves. At low magnifications, plaque really does resemble some kind of dead, fatty, precipitate, stuck to the inside wall of arteries. However, in histological sections at higher magnifications, you can easily and unambiguously see that plaque is irregularly distributed among the smooth muscle cells of which artery walls are made, and consists of still-living smooth muscle cells, mixed with highly vacuolated macrophages, cholesterol, precipitated calcium salts and other materials.

As these mixtures of materials increase in volume, they push inward on the endothelium layer inside which blood flows. Blockage gradually worsens, usually without symptoms, until 50%, 60% up to 90% or more of normal blood flow becomes obstructed. Then blood clots tend to form at the narrowest constrictions, often cutting off nearly all blood supply, thereby causing "ischemic" death of substantial volumes of heart, brain, kidney or other tissues. In addition, fragments of atherosclerotic artery walls often break loose, get carried away in the blood flow, then get stuck at some other narrowed location, depriving tissues of oxygen.

Formation of atherosclerotic plaque is stimulated (= increased in amount; caused to form earlier in life) by high blood pressure, smoking, obesity and higher than normal concentrations of cholesterol (solubilized in the blood by any of several special lipid-protein complexes).

Note however, that cholesterol is a normal (and also necessary) component of the human body. We have enzymes whose specific function is to synthesize cholesterol, and others whose functions are to reabsorb cholesterol from intestinal contents. Cholesterol synthesizing enzymes are selectively inhibited by a family of synthetic chemicals called statins. These enzyme inhibitors are structural analogs of a necessary stage of synthesis of steroids, which is how they selectively block cholesterol synthesis. Another way to decrease amounts of cholesterol in the blood is by chemicals that inhibit its resorption from the blood. Cholesterol is a major component in bile, serving as a detergent. Anti-cholesterol drugs are genuinely effective inhibitors of atherosclerosis.

Please be ready and willing to describe whatever opinions you have about the following 7 quotes from Wikipedia articles:

" Statins are particularly well suited for lowering LDL, the cholesterol with the strongest links to vascular diseases."

"There is a risk of severe muscle damage (myopathy &rhabdomyolysis) with statins."

"Fibrates reduce the number of non-fatal heart attacks, but do not improve all-cause mortality"

Since fibrates increase the cholesterol content of bile, they increase the risk for gallstones."

"Fibrates have been shown to extend lifespan in the roundworm C. elegans"

[For treating Muscular Dystrophy] "medications used include steroids to slow muscle degeneration... … and immunosuppressants to delay damage to dying muscle cells " [in muscular dystrophy patients]