Basic Causes of Atherosclerosis - The Roles of Cholesterol and Lipoproteins
Increased Low-Density Lipoproteins. An important factorin causing atherosclerosis is a high blood plasma concentration of cholesterol in the form of low-density lipoproteins. The plasma concentration of these high-cholesterol low-density lipoproteins is increased by several factors, including eating highly saturated fat in the daily diet, obesity, and physical inactivity. To a lesser extent, eating excess cholesterol may also raise plasma levels of low-density lipoproteins.
An interesting example occurs in rabbits, which normally have low plasma cholesterol concentrations because of their vegetarian diet. Simply feeding these animals large quantities of cholesterol as part of their daily diet leads to serious atherosclerotic plaques throughout their arterial systems.
Familial Hypercholesterolemia.This is a disease in whichthe person inherits defective genes for the formation of low-density lipoprotein receptors on the membrane sur-faces of the body’s cells. In the absence of these recep-tors, the liver cannot absorb either intermediate-density or low-density lipoproteins. Without this absorption, the cholesterol machinery of the liver cells goes on a rampage, producing new cholesterol; it is no longer responsive to the feedback inhibition of too much plasma cholesterol. As a result, the number of very low density lipoproteins released by the liver into the plasma increases immensely.
Patients with full-blown familial hypercholes-terolemia have blood cholesterol concentrations of 600 to 1000 mg/dl, levels that are four to six times normal. Many of these people die before age 20 because of myocardial infarction or other sequelae of atheroscle-rotic blockage of blood vessels throughout the body.
Role of High-Density Lipoproteins in Preventing Atherosclerosis.
Much less is known about the function of high-density lipoproteins compared with that of low-density lipopro-teins. It is believed that high-density lipoproteins can actually absorb cholesterol crystals that are beginning to be deposited in arterial walls. Whether this mecha-nism is true or not, high-density lipoproteins do help protect against the development of atherosclerosis. Consequently, when a person has a high ratio of high-density to low-density lipoproteins, the likelihood of developing atherosclerosis is greatly reduced.
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