Considerations in the Use of Mouse Models of Vascular and Valvular Calcification

CLINICAL PROBLEM: Vascular and valvular calcification significantly contributes to cardiovascular morbidity, particularly in patients with diabetes, atherosclerosis, advanced age, and chronic kidney disease. Currently, there are no effective treatments to prevent or reverse calcification, emphasizing the urgent need for robust preclinical models to help identify therapeutic targets and strategies. RECOMMENDATIONS: Preclinical models for vascular and valvular calcification should accurately reflect human disease pathology and progression, ideally including the influence of key underlying conditions and diseases (age, diabetes, renal disease, and hyperlipidemia), as well as sexual dimorphism, each of which may require a different model. Standardized and reproducible end points are essential, with preference for assessments that align with clinically utilized modalities (eg, computed tomography and echocardiography). SUMMARY: Murine models of cardiovascular calcification described herein have contributed substantially to our understanding of cardiovascular calcification though the translation toward clinically impactful therapies has, thus far, been limited. Improving clinical translation demands the use of models that replicate human comorbidities, disease progression, and outcomes. Further development of improved models, particularly those that demonstrate clinically important features such as plaque rupture, will facilitate effective translation of therapeutic strategies to clinical practice.