Abstract
Precise quantification of atherosclerotic plaque in preclinical models of atherosclerosis requires the volumetric assessment of the lesion(s) while maintaining in situ architecture. Here we use micro-computed tomography (microCT) to detect ex vivo aortic plaque established in three dyslipidemic mouse models of atherosclerosis. All three models lack the low-density lipoprotein receptor (Ldlr−/−), each differing in plaque severity, allowing the evaluation of different plaque volumes using microCT technology. From clearly identified lesions in the thoracic aorta from each model, we were able to determine plaque volume (0.04–3.1 mm3), intimal surface area (0.5–30 mm2), and maximum plaque (intimal-medial) thickness (0.1–0.7 mm). Further, quantification of aortic volume allowed calculation of vessel occlusion by the plaque. To validate microCT for future preclinical studies, we compared microCT data to intimal surface area (by using en face methodology). Both plaque surface area and plaque volume were in excellent correlation between microCT assessment and en face surface area (r2 = 0.99, p<0.0001 and r2 = 0.95, p<0.0001, respectively). MicroCT also identified internal characteristics of the lipid core and fibrous cap, which were confirmed pathologically as Stary type III-V lesions. These data validate the use of microCT technology to provide a more exact empirical measure of ex vivo plaque volume throughout the entire intact aorta in situ for the quantification of atherosclerosis in preclinical models.
Highlights
Ischemic heart disease resulting from coronary atherosclerosis is the leading cause of human mortality worldwide [1,2]
We evaluated whether the lesion measurements between Ldlr2KO and -3KO aortas generated with micro-computed tomography (microCT) showed similar fold differences with en face (Figure S3) and found a 14.6-fold difference in total plaque surface area between Ldlr-2KO and Ldlr3KO using en face and a 17.5-fold difference using microCT (Figure S3A), demonstrating comparable fold differences between the two techniques
The microCT methodology presented clearly detected aortic lesions in all three Ldlr -deficient models, providing data that can be processed to generate movies to view the relevant features from any orientation
Summary
Ischemic heart disease resulting from coronary atherosclerosis is the leading cause of human mortality worldwide [1,2]. One method requires the sequential sectioning of the heart and aortic root [3] and subsequent histopathologic analysis to score and measure lesions in a 300 micron area at the level of the aortic sinus Another method employs Sudan IV staining to determine the extent of atherosclerosis affecting the intimal surface throughout the entire aorta [4]. The technique consists of dissecting the aorta from the heart to the iliac bifurcation, opening it longitudinally to expose the luminal side, and staining it with Sudan IV to reveal lipid-laden plaques to measure lesional surface areas. These two methods provide qualitatively distinct estimates of lesion area in orthogonal axes. Despite the advancements in assessing aortic plaque, the need remains for the generation of very high-resolution three-dimensional plaque models, along with determining the degree of occlusion
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call