Atherosclerotic Plaque Destabilization in Mice: A Comparative Study

Abstract

Atherosclerosis-associated diseases are the main cause of mortality and morbidity in western societies. The progression of atherosclerosis is a dynamic process evolving from early to advanced lesions that may become rupture-prone vulnerable plaques. Acute coronary syndromes are the clinical manifestation of life-threatening thrombotic events associated with high-risk vulnerable plaques. Hyperlipidemic mouse models have been extensively used in studying the mechanisms controlling initiation and progression of atherosclerosis. However, the understanding of mechanisms leading to atherosclerotic plaque destabilization has been hampered by the lack of proper animal models mimicking this process. Although various mouse models generate atherosclerotic plaques with histological features of human advanced lesions, a consensus model to study atherosclerotic plaque destabilization is still lacking. Hence, we studied the degree and features of plaque vulnerability in different mouse models of atherosclerotic plaque destabilization and find that the model based on the placement of a shear stress modifier in combination with hypercholesterolemia represent with high incidence the most human like lesions compared to the other models.

Resolving Lipid Mediators Maresin 1 and Resolvin D2 Prevent Atheroprogression in Mice

“…When integrating these parameters into a vulnerability plaque index (VPI), essentially a quotient of destabilizing (macrophages and necrotic core size) and stabilizing (smooth muscle cells and collagen) parameters, an integral impression of plaque stability can be derived. 27 In addition, endothelial activation was assessed by the measurement of ICAM1 (intercellular adhesion molecule 1)-and VCAM1 (vascular cell adhesion molecule 1)-positive endothelial lining.…”

Semi-Automated Curation Allows Causal Network Model Building for the Quantification of Age-Dependent Plaque Progression in ApoE–/– Mouse

“…This study compared the aorta transcriptomes of C57BL6/J and ApoE −/− knockout mice at different ages. In the ApoE −/− genetic background, age is considered a biological stimulus of atherogenesis and a strong inducer of the mechanisms implicated in the atherosclerotic destabilization process 24. The 6-week-old ApoE −/− mice described in the GSE10000 data set had minor atherosclerotic lesions that advanced with time to become the advanced atherosclerotic lesions observed in the aorta of 32- and 78-week-old mice 24.…”

“…In the ApoE −/− genetic background, age is considered a biological stimulus of atherogenesis and a strong inducer of the mechanisms implicated in the atherosclerotic destabilization process 24. The 6-week-old ApoE −/− mice described in the GSE10000 data set had minor atherosclerotic lesions that advanced with time to become the advanced atherosclerotic lesions observed in the aorta of 32- and 78-week-old mice 24. The GSE9371 (http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE9371) data set examined the implication of alpha and beta estrogen receptors in mouse arteries.…”

High Dose MicroCT Does Not Contribute Toward Improved MicroPET/CT Image Quantitative Accuracy and Can Limit Longitudinal Scanning of Small Animals

“…Moreover, diagnostic and therapeutic agents can be developed and tested on identical platforms, accelerating the translational process to humans [2]. Hence, efforts toward optimization of microPET/CT acquisition and reconstruction protocols will have a widespread impact across several biomedical fields, including: biomarker research [1,[3][4][5], and research in neurodegenerative diseases, cardiovascular diseases [6][7][8][9][10], metabolic diseases, musculoskeletal disorders and oncology [11][12][13][14].…”