Understanding Atherosclerosis
Atherosclerosis is a chronic inflammatory disease of the arterial wall characterized by lipid accumulation, immune cell infiltration, and plaque formation. Mouse models enable controlled study of disease mechanisms.
Disease Progression
Fatty Streak Formation
Early lesions with lipid laden macrophages (foam cells) in the intima.
Plaque Development
Progressive accumulation of lipids, inflammatory cells, and smooth muscle cells. Formation of fibrous cap.
Advanced Lesions
Necrotic core development, calcification, and potential for plaque rupture and thrombosis.
Key Pathogenic Mechanisms
Atherosclerosis Model Types
ApoE Knockout Model
The most widely used atherosclerosis model. Apolipoprotein E mediates hepatic clearance of lipoprotein remnants. Loss causes accumulation of atherogenic lipoproteins.
- Marked hypercholesterolemia (~400 mg/dL on chow, higher on Western diet)
- Elevated VLDL and IDL
- Fatty streaks visible by 10 weeks on chow
- Advanced plaques with Western diet
LDLR Knockout Model
Alternative lipoprotein metabolism model. LDL receptor clears LDL cholesterol from circulation. Loss causes LDL accumulation similar to human familial hypercholesterolemia.
- Elevated LDL cholesterol on high fat/high cholesterol diet
- More similar to human lipid profile than ApoE knockout
- Minimal lesions on chow diet
- Robust atherosclerosis on Western diet
Conditional Approaches
Cell type specific gene manipulation enables dissection of contributions from different vascular and immune cell populations.
Vascular Endothelium
- •Cdh5 Cre (VE Cadherin Cre): Endothelial cell specific deletion
- •Tie2 Cre: Endothelial and hematopoietic lineages
Macrophages
- •LysM Cre: Myeloid cell targeting for foam cell studies
- •CX3CR1 Cre: Monocyte/macrophage specific
Smooth Muscle
- •SM22 Cre (Tagln Cre): Smooth muscle cell specific deletion
- •Myh11 Cre: Alternative smooth muscle driver
Hepatocytes
- •Albumin Cre: Liver specific for lipid metabolism genes
Phenotyping Atherosclerosis Models
Lipid Analysis
- •Plasma lipids: Total cholesterol, triglycerides, HDL, LDL
- •Lipoprotein fractionation: FPLC or ultracentrifugation
- •Lipid staining: Oil Red O or Sudan IV
Lesion Quantification
- •En face aorta: Sudan IV stained aorta for total lesion area
- •Aortic root sections: Serial sections at aortic valve level
- •Brachiocephalic artery: Cross sections for advanced lesions
Lesion Characterization
- •Histology: H&E, trichrome for fibrosis, von Kossa for calcification
- •Immunohistochemistry: Macrophage markers, smooth muscle actin
- •Lesion composition: Necrotic core, fibrous cap thickness
Selected Publications in Atherosclerosis Research
Recent publications demonstrate the utility of genetically engineered mouse models in cardiovascular research:
Zong P, Li CX, Feng J, Yue Z, Nethramangalath T, Xie Y, Qin X, Cicchetti M, Cai Y, Jellison E, Matsushita M, Runnels LW, Yue L. (2025).
TRPM7 channel activity promotes the pathogenesis of abdominal aortic aneurysms ↗Nat Cardiovasc Res 4(2): 197-215
Xu J, Choi R, Gupta K, Warren HR, Santhanam L, Pluznick JL. (2024).
An evolutionarily conserved olfactory receptor is required for sex differences in blood pressure ↗Science Advances 12(10): eadk1487
What Researchers Say
“iTL generated our angiotensin II type 1a receptor conditional mouse. We found this company very responsive. The project started with discussions on possible construct designs. Following approval, a project manager sent monthly reports alerting us to project milestones. Our experience with iTL was so positive that we have generated more conditional mice with them.”
— Debra Rateri, BS
University of Kentucky
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