Influence of Hypercholesterolemia and Adventitial Inflammation on the Development of Aortic Aneurysm in Rabbits

Abstract

Abdominal aortic aneurysms are characterized by intimal atherosclerosis, disruption and attenuation of the elastic media, and a variable adventitial inflammatory infiltrate. We have developed an animal model of this disorder to evaluate the contribution of hypercholesterolemia, medial injury, and adventitial inflammation to aneurysmal dilatation. To accomplish this, we used periaortic application of calcium chloride, which induced both medial injury with calcification and endothelial injury. Ultrasonography was used to demonstrate the dilatation and thickening of the aortic wall. Over the first 3 weeks after periaortic application of 0.25 mol/L CaCl2, the external aortic diameter increased from 3.5±0.5 to 4.2±0.8 mm, but the ID remained unchanged. This apparent wall thickening was accompanied by vascular remodeling, and biochemical changes included ≈50% reduction in tissue hydroxyproline concentration and increased activity of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9). Independently, choles...