Individuals with diabetes mellitus face an increased risk of developing atherosclerosis, the most common cause of peripheral arterial disease (PAD). At Ace Therapeutics, we specialize in offering modeling services for diabetes-associated atherosclerosis. Our animal models help researchers study the pathological mechanisms underlying this condition and discover mechanism-based targeted therapies to alleviate the burden of diabetes complications.

Overview of Diabetic Atherosclerosis

Atherosclerosis, one of the main complications of diabetes, is the leading cause of death and disability in individuals with diabetes. Key factors to consider when selecting an animal model for diabetes-associated atherosclerosis include hyperglycemia, dyslipidemia, oxidative stress, inflammation, and endothelial dysfunction. Hyperglycemia triggers pro-inflammatory and pro-oxidant pathways, leading to molecular, cellular, and vascular damage. Dyslipidemia in diabetes is characterized by elevated triglycerides, decreased HDL cholesterol, and changes in LDL structure, promoting a more atherogenic profile. In addition, hyperglycemia-induced endothelial dysfunction and reduced nitric oxide production contribute to impaired blood flow and increased atherogenesis. These factors, combined with oxidized LDL particles, promote leukocyte adhesion, foam cell formation, and accelerate the progression of atherosclerosis.

Fig. 1. The stages of atherosclerotic plaque development. (Siracuse J J, et al., 2012)

Our Modeling Services for Atherosclerosis

At Ace Therapeutics, our research team employs genetic manipulation techniques—such as deletion of the apolipoprotein E (ApoE) gene or the low-density lipoprotein receptor (LDLR) gene—alongside dietary interventions to simulate atherosclerotic plaque development, supporting our clients' studies in this domain. We provide widely recognized mouse models of diabetes-related atherosclerosis, available at every stage of disease progression, including:

Early stage: Characterized by endothelial dysfunction, oxidative stress and inflammation, leukocyte-endothelial interactions, and plaque formation.

Advanced Phase: Characterized by Necrotic core, smooth muscle cell migration, fibrous cup, and vulnerable plaque.

Plaque Rupture: Characterized by unstable plaque and thrombosis.

• ApoE^-/-Fbn1^c1039g+/- + western diet, ApoE^-/- + western diet by placing perivascular carotid cuff or ligation of the common carotid arteries, Tandem Stenosis ApoE^-/- + western diet

Our Services for Diabetic Atherosclerosis Research

To effectively evaluate the efficacy of potential drug candidates for diabetes-associated atherosclerosis, it is essential to employ appropriate technologies for analyzing animal models. We offer comprehensive analytical services that empower our clients to gain a deep understanding of disease progression.

• Plaque visualization: MicroCT, 3D MRI, Fluorescence emission computed technology
• Plaque quantification: En face Sudan IV, Oil red O
• Characterization of cellular components in atherosclerotic plaques: H&E, Picosirius red, Masson's trichrome, IHC/IF
• Inflammatory and oxidative stress markers: Western blot, IHC/IF, ELISA, PCR, LCM
• Cell-specific markers or transcriptomes: Flow cytometry, scRNAseq, CyTOF, ATAC-seq, CITE-seq
• Endothelial dysfunction: Vessel myography
• Leukocyte-endothelial interactions: Intravital microscopy

Please do not hesitate to contact us if you wish to know more about how our services can be tailored according to your needs. You will be able to precisely mimic the disease and investigate vascular inflammation along with testing potential therapies by using our animal models in combination with the described advanced techniques.

Reference

1. Siracuse J J, Chaikof E L. (2012) The pathogenesis of diabetic atherosclerosis. Diabetes and Peripheral Vascular Disease: Diagnosis and Management. 13-26.

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