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.
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.