Atherosclerosis Model

Indication and Application:

Efficacy screening of novel antihyperlipidemic and lipid-lowering drugs (e.g., Statins, PCSK9 inhibitors, siRNA therapies), evaluation of anti-inflammatory compounds targeting plaque stability, validation of intravascular imaging technologies (IVUS, OCT), and research on macrophage polarization and foam cell formation.

Modeling Method:

• Genetically Induced Model (Rodents): ApoE-/- or LDLR-/- mice are maintained on a standardized high-cholesterol Western Diet (typically 21% fat, 0.15% to 1.25% cholesterol) for 8 to 16 weeks to induce widespread, systemic atheromatous plaques throughout the aortic arch and abdominal aorta.

• Combination Injury Model (Large Animal/Rabbit): A combination of endovascular balloon denudation of the carotid or femoral artery followed by an atherogenic diet is utilized to generate advanced, focal atheromatous lesions with high translational fidelity for medical device or late-stage therapeutic testing.

Clinical Relevance:

• Pathological and Kinetic Fidelity: The model successfully recapitulates the sequential stages of human clinical atherosclerosis, progressing from endothelial dysfunction and lipid accumulation to foam cell infiltration, fibrous cap development, and intra-plaque calcification or necrosis.

• Translational Efficacy Platform: The presence of highly complex plaques makes this model an indispensable tool for evaluating the systemic clearance of low-density lipoprotein cholesterol (LDL-C) and the localized morphological stabilization of vulnerable plaques prior to clinical trial transition.

Key Evaluation Endpoints:

1. In Vivo / Surgical / Imaging:

• Serum Lipid Profiling: Comprehensive quantification of Total Cholesterol (TC), Triglycerides (TG), Low-Density Lipoprotein Cholesterol (LDL-C), and High-Density Lipoprotein Cholesterol (HDL-C) over longitudinal time points.

• High-Resolution Optical Coherence Tomography (OCT) or Intravascular Ultrasound (IVUS): High-fidelity in vivo visualization of plaque burden, lumen narrowing, and fibrous cap thickness.

2. Histopathology:

• En Face Aorta Quantitation (Gold Standard): Oil Red O or Sudan IV staining of the entire pinned-out aorta to quantify the percentage of cumulative surface area covered by atherosclerotic plaques.

• Plaque Composition Profiling: Cross-sectional H&E and Masson's Trichrome staining of the aortic root or target vessels to measure lesion size, necrotic core areas, and collagen content.

• Plaque Vulnerability Index: Quantitative measurement of the ratio between lipid/macrophage content and collagen/smooth muscle cell content.

• IHC/IF: Analysis of foam cell and macrophage infiltration (CD68, F4/80), smooth muscle cell migration (alpha-SMA), and endothelial status (CD31).

3. Molecular:

• Expression profiles of pro-inflammatory cytokines (IL-1beta, TNF-alpha, IL-6, MCP-1) and matrix metalloproteinases (MMP-2, MMP-9) via RT-qPCR, ELISA, or Western Blot to evaluate the systemic and vascular anti-inflammatory efficacy of test compounds.

Regulatory-Grade Data Package (OECD GLP, AAALAC, CMA, CNAS): 

As an established preclinical CRO, all metabolic and cardiovascular studies at HuaTeng Biotechnology are executed under rigorous international quality parameters. Our standardized breeding, high-fat diet compliance metrics, and automated image analysis suites significantly eliminate experimental drift. We deliver tightly grouped data packages specifically formatted to support global IND and regulatory filings for pharmaceutical innovators worldwide.