Development of a Novel Murine Model of In-Stent Neoatherosclerosis

Area of Science:

• Cardiovascular Research
• Translational Medicine
• Animal Models

Background:

• In-stent neoatherosclerosis is a post-stenting complication developing within 1-5 years.
• Current lack of preclinical small animal models hinders research into neoatherosclerosis biology and therapies.

Purpose of the Study:

• Establish and validate a novel murine model for in-stent neoatherosclerosis.
• Provide a platform for studying disease mechanisms and evaluating targeted treatments.

Main Methods:

• Stainless-steel stents implanted in donor aortas of apolipoprotein E-deficient (Apoe-/-) mice, then grafted into recipients.
• Mice fed high-cholesterol diet post-surgery; stented vessels assessed using bimodal intravascular imaging (OCT and fluorescence) and histology.
• Flow cytometry used to analyze cellular content of stented aortas.

Main Results:

• Bimodal imaging visualized in-stent neoatherosclerosis, including plaque burden and instability.
• High-cholesterol diet induced neointimas with lipid cores and macrophages, mimicking human neoatherosclerosis.
• Distinct neointimas (smooth muscle cell-rich) observed in mice on chow diet, resembling neointimal hyperplasia.

Conclusions:

• Successfully developed and validated the first murine model of human in-stent neoatherosclerosis.
• This model is crucial for investigating neoatherosclerosis pathogenesis.
• Enables preclinical testing of novel therapeutic strategies for in-stent neoatherosclerosis.