Atherosclerosis model testing provides systematic evaluation of atherosclerotic lesion development, plaque stability, lipid metabolism, and inflammatory biomarkers in validated animal and cellular models. These testing services support cardiovascular drug development, functional food assessment, and mechanistic research by delivering quantitative, reproducible, and GLP-compliant analytical data. Accredited third-party laboratories offer end-to-end solutions ranging from model establishment to histopathological and molecular endpoint analysis.
Technical Overview
Atherosclerosis is a chronic progressive vascular disease characterized by lipid accumulation, chronic inflammation, endothelial dysfunction, and smooth muscle cell proliferation within arterial walls. Reliable evaluation of experimental atherosclerosis models is essential for preclinical cardiovascular research, lipid-lowering drug screening, and functional food efficacy studies. Atherosclerosis model testing encompasses the induction and validation of disease models, quantification of atherosclerotic lesions, characterization of plaque composition and stability, and measurement of associated biochemical and molecular biomarkers.
Commonly used models include ApoE-deficient (ApoE-/-) mice, LDL receptor-deficient (LDLR-/-) mice, high-fat diet-induced rodent models, and cholesterol-fed rabbit models such as New Zealand white rabbits. Testing procedures are typically conducted in accordance with Good Laboratory Practice (GLP) principles, the ARRIVE guidelines for animal research reporting, and relevant national laboratory animal standards such as GB 14925 governing animal care and housing environments. All studies are reviewed by institutional animal ethics committees to ensure humane and scientifically justified experimental design.
Testing Samples
Animal Model Blood and Serum Samples
Blood, serum, and plasma samples are collected from atherosclerosis model animals at predefined time points for lipid profile analysis, inflammatory cytokine quantification, and liver and kidney function assessment. Samples may be collected at baseline, mid-study, and terminal endpoints to track disease progression and therapeutic intervention effects.
Vascular Tissue Samples
Aortic root, aortic arch, brachiocephalic artery, and full-length aorta samples are harvested for histological and morphometric analysis. Both paraffin-embedded and frozen tissue sections are prepared to support standard and lipid-sensitive staining protocols. En face aorta preparations allow whole-vessel lesion burden quantification across the entire arterial tree.
Organ and Cell Samples
Liver, heart, kidney, and spleen tissues are collected for histopathological evaluation of lipid deposition and off-target effects. In vitro foam cell models, derived from macrophages treated with oxidized low-density lipoprotein (ox-LDL), and endothelial cell models are also accepted for cellular lipid accumulation and functional assays.
Testing Items
Atherosclerosis model testing typically covers the following analytical categories:
- Serum lipid profile: total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), very-low-density lipoprotein (VLDL), apolipoprotein A1 (ApoA1), apolipoprotein B (ApoB), and free fatty acids
- Plaque burden quantification: lesion area at the aortic valve, en face total lesion area, lumen stenosis rate, and plaque-to-lumen ratio
- Plaque composition and stability: lipid core area, fibrous cap thickness, collagen content, smooth muscle cell density, macrophage content, and necrotic core analysis
- Inflammatory biomarkers: C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1)
- Oxidative stress markers: oxidized LDL (ox-LDL), superoxide dismutase (SOD), malondialdehyde (MDA), glutathione (GSH), and total antioxidant capacity
- Liver and kidney function: alanine aminotransferase (ALT), aspartate aminotransferase (AST), creatinine, and urea nitrogen
- Molecular endpoints: target gene expression by quantitative real-time PCR, protein expression by Western blot and immunohistochemistry, and macrophage polarization markers
Testing Methods
A comprehensive analytical platform is applied to ensure accurate and reproducible quantification of atherosclerotic endpoints:
- Automated biochemistry analysis: enzymatic and colorimetric assays performed on automated analyzers for serum lipid and organ function parameters, following CLSI-recommended analytical protocols
- Oil Red O staining: performed on frozen aortic sections to visualize neutral lipid deposits within plaques and quantify lipid-positive lesion areas
- Hematoxylin and eosin (H&E) staining: used for overall plaque morphology, lesion classification, and general histopathology of major organs
- Masson's trichrome and Sirius red staining: applied to quantify collagen content and evaluate fibrous cap integrity as indicators of plaque stability
- Immunohistochemistry and immunofluorescence: detection of CD68 for macrophages, alpha-SMA for smooth muscle cells, and VCAM-1 for endothelial activation within plaque tissue
- En face aortic analysis: Sudan IV or Oil Red O staining of the opened whole aorta to measure total and regional lesion coverage by image analysis
- ELISA: quantitative measurement of serum cytokines, adhesion molecules, and oxidation biomarkers using validated immunoassay kits
- Quantitative real-time PCR and Western blot: semi-quantitative and quantitative assessment of gene and protein expression related to lipid metabolism, inflammation, and signaling pathways
Applications
Atherosclerosis model testing services are widely applied across pharmaceutical, nutraceutical, and academic research settings:
- Preclinical efficacy evaluation of lipid-lowering, anti-inflammatory, anti-oxidative, and plaque-stabilizing drug candidates
- Efficacy substantiation for functional foods, dietary supplements, and natural bioactive compounds targeting cardiovascular health
- Evaluation of traditional herbal medicine formulations for blood lipid regulation and vascular protection
- Mechanistic studies of disease progression, including foam cell formation, endothelial dysfunction, and inflammatory signaling pathways
- Safety and tolerability assessment supporting investigational product development under GLP-aligned study designs
- Publication-ready data packages with full statistical analysis, image documentation, and method validation records
FAQ
How long does it take to establish a typical atherosclerosis model?
ApoE-/- mice fed a Western-type high-fat diet generally develop measurable aortic root lesions within 8 to 12 weeks, with advanced plaques observed after 16 to 24 weeks. High-fat diet-induced models in wild-type rodents typically require longer induction periods and are often complemented by vitamin D3 or vascular injury protocols.
Which model is most appropriate for my study?
ApoE-/- mice fed a high-fat diet are the most widely used model due to rapid and reproducible lesion development across the aortic root, arch, and whole aorta. LDLR-/- mice better reflect human-like lipoprotein metabolism, while rabbit models are preferred when larger vessels are required for stent or device evaluation. Study design consultation with accredited third-party laboratories helps align model selection with research objectives.
What sample conditions are required for shipping?
Serum and plasma samples should be frozen and shipped on dry ice with temperature monitoring. Fresh tissues intended for frozen sectioning should be embedded in optimal cutting temperature compound and snap-frozen, while paraffin-embedded blocks and stained slides can be shipped at ambient temperature. Detailed shipping guidelines are provided before sample dispatch.
What deliverables are included in the final report?
Standard deliverables include a comprehensive study report containing experimental protocols, raw analytical data, histological images with quantitative morphometry, statistical analysis, and conclusions. Reports are structured to support regulatory submissions, product claims substantiation, and peer-reviewed publication.
Are study designs compliant with animal welfare requirements?
Yes. All animal studies follow the principles of the 3Rs (replacement, reduction, and refinement), are approved by institutional animal care and use committees, and are conducted in facilities meeting national laboratory animal standards such as GB 14925 for housing and environmental control.