Quantitative Analysis of the Development of Experimental Atherosclerosis in the Dog

Atherosclerosis was produced in dogs by feeding them thiouracil and cholesterol. The increments in cholesterol concentration at sites along the length of the aortas of these dogs Avere determined by subtracting from the value for each site the corresponding value obtained from normal dogs. After about 1 month on the experimental regimen the cholesterol increments along the length of the aorta formed a gradient. The increment was greatest in the proximal aorta and progressively less down the length of the aorta. After about 5 months on the regimen, the gradient no longer existed. Instead, the cholesterol increment in the abdominal aorta exceeded that in the thoracic aorta. Albumin is known to enter aortic wall with a gradient of rates that is similar to the gradient of cholesterol increments early in the course of experimental atherosclerosis. The foregoing facts are consistent with the following theory: In the development of atherosclerosis, intact low-density lipoproteins containing cholesterol enter the aortic wall with a gradient of rates. They enter fastest in the proximal aorta and progressively less rapidly down the length of the aorta. However, cholesterol is removed from the abdominal aorta much more slowly than from the thoracic aorta. Thus, the increment in cholesterol concentration in the abdominal aorta eventually exceeds that in the thoracic aorta.