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 approximately 50% reduction in tissue hydroxyproline concentration and increased activity of gelatinases (matrix metalloproteinase [MMP]-2 and MMP-9). Independently, cholesterol feeding to induce hypercholesterolemia or the concomitant periaortic application of thioglycollate had little effect on the histological, biochemical, or diameter changes. Together, hypercholesterolemia and thioglycollate were associated with rapid aortic dilatation in CaCl2, treated animals but not controls: after 3 weeks, the ID and OD had doubled, the OD increasing from 3.5 +/- 0.4 to 7.1 +/- 0.4 mm, P = .005. The remarkable feature that accompanied this dilatation was the infiltration of cells, mostly foamy macrophages, into the adventitia, with a further reduction in hydroxyproline concentration. Adventitial inflammation may provide the critical stimulus to dilatation of an aorta with preexisting intimal and medial injury.

Morphometry and Vascularization of the Rabbit Kidneys (Oryctolagus cuniculus)

“…This information can be applied not only to domestic animals but also to humans (Cizkova et al, 2001). Furthermore, as an excellent model species, rabbits help to investigate such conditions like arterial injury (Jorgensen et al, 1972), aortic occlusion (Mackey et al, 1997) and aortic aneurysm (Freestone et al, 1997). However, there is limited information about basic anatomy of the rabbit kidney.…”

Unique Phenotypes of Endothelial Cells in Developing Arteries: A Lesson from the Ductus Arteriosus

“…For instance, a wire injury model is used for studying pathology of endothelial injury/dysfunction [5]; low-density lipoprotein receptor-deicient mice [6] and apolipoprotein E-deicient mice [7] are commonly used as atherosclerosis models; calcium chloride [8], elastase [9], angiotensin II [10], or microRNA-21 [11] are infused to create an abdominal aortic aneurysms model. Developing a disease model occupies a great deal of scientiic indings on pathophysiology, and so the existing models should always open to be reined.…”

Clinical Impact of Hemorheology Assessed Using the Microchannel Array Flow Analyzer on Renal Resistive Index in Patients With Type 2 Diabetes Mellitus

“…Hemorheology was assessed by measuring WBPT using an MC-FAN HR300 rheometer (MC Healthcare Inc., Tokyo, Japan), as previously reported [6,10]. The microchannel passage time for 100 µL of physiological saline as a control was initially measured, followed by that for 100 µL of heparinized blood samples obtained from the study participants.…”

“…MC-FAN has a simple methodology and is superior to other methods regarding the accuracy of channel dimensions and high reproducibility. Furthermore, some clinical studies have reported a significant relationship between an increase in the whole blood passage time (WBPT), which is measured using MC-FAN, and cardiovascular risk factors or coronary artery disease [7][8][9][10][11].…”