Electronic Thesis and Dissertation Repository

Degree

Doctor of Philosophy

Program

Anatomy and Cell Biology

Supervisor

Dr. Kem A. Rogers

2nd Supervisor

Dr. Derek R. Boughner

Joint Supervisor

Abstract

Aims: Three types of cardiovascular calcification are commonly found in humans: arterial calcification, intimal calcification, and calcific aortic valve disease. Very little is known about the mechanisms driving cardiovascular calcification despite serious clinical implications and a clear association with morbidity and mortality. Indeed, it is even unclear whether the same factors are involved in arterial, intimal, and valvular calcification. The objective of this study was to elucidate the effects of an angiotensin II type 1 receptor blocker (ARB) on the progression of cardiovascular calcification in male New Zealand White rabbits. Where appropriate, statins were examined in conjunction and in combination with ARBs.

Methods and Results: In vivo and ex vivo techniques were used to assess overall disease burden and the extent of calcification including magnetic resonance imaging, micro-computed tomography, histology, and immunohistochemistry. ARB administration significantly inhibited progression of arterial calcification (2.80 ± 1.17 versus 0.01 ± 0.01 % calcified tissue in Cholesterol and ARB-treated, respectively; P < 0.05), but not intimal or valvular calcification. ARB treatment significantly reduced atherosclerotic lesion area when delivered alone (95.50 ± 1.94 versus 61.61 ± 10.17 % lesion area in Cholesterol and ARB-treated, respectively; P < 0.05), but not when combined with statin therapy (92.39 ± 3.25 % in ARB+Statin; P < 0.05 when compared to ARB monotherapy). Finally, ARB-treated animals had significantly increased valvular calcium.

Conclusions: This study provides evidence that ARBs robustly inhibit arterial calcification and is the first to suggest ARBs as a novel treatment option for those at risk for cardiovascular calcification. It also suggests that ARBs may not be beneficial for those at risk for intimal or valvular calcification. These disparate results suggest that the three types of cardiovascular calcification are distinct from one another and provides impetus to further examine the underlying molecular mechanisms at play in these debilitating disease processes.

Download

Share

COinS