Table 1 Advantages and disadvantages of CAVD animal models

Diet-induced animal models

mouse

42% fat, 0.15 ~ 0.2% cholesterol, 1.2% choline, 2 ~ 16 m (Aikawa et al. 2009; Hakuno et al. 2010; Jung et al. 2015; Li et al. 2022; Matsumoto et al. 2010; Miller et al. 2010; Nigam & Srivastava 2009; The et al. 2022; Towler et al. 1998; Yanget al. 2021; Zeadin et al. 2009)

susceptible to genetic manipulation; Relatively cheap and easy to house; Short lifespan

Limited similarity to human disease; Small size

rabbit

0.5% ~ 2% cholesterol, VitD2 25,000/50,000/100,000 IU /day, 2 ~ 12 w (Arishiro et al. 2007; Choi et al. 2021; Cimini et al. 2005; Drolet et al. 2008; Gkizas et al. 2010; Haberland et al. 2001; Hamilton et al. 2011; Liberman et al. 2008; Marechaux et al. 2009; Ngo et al. 2011; Rajamannan et al. 2005; Zeng et al. 2007)

Rapid disease progression; Small size and ease of handling; Availability of reagents and tools;

Amenable to genetic manipulation

The anatomy and hemodynamics of rabbit hearts differ from those of humans; challenging to control experimental variables

swine

12 ~ 15% lard, 1.5% cholesterol, 32% fat, 2 ~ 6 m (Guerraty et al. 2010; Sider et al. 2014; Simmons et al. 2005)

Similar in size, structure, function, and hemodynamics to human hearts; Spontaneously develop CAVD similar to humans

Limited availability of standardized models; Challenging to control experimental variables;

Potential for species-specific differences

Genetically modified animal models

Apoe − / − mice (Aikawa et al. 2009; Hjortnaes et al. 2010; Srivastava et al. 2011; Tanaka et al. 2005; Zeadin et al. 2009);

LDLr(-/-)mice (Dharmarajan et al. 2021; Gao et al. 2021; Liu et al. 2022; Schlotter et al. 2012); klotho-deficient mice (Wirrig et al. 2015)

enabling mechanistic and therapeutic target discovery; Mimics calcification & valvular dysfunction

Expensive and time-consuming; Off-target effects; Limited scope

Mechanical injury models

A direct balloon injury to the aortic valve (Kim et al. 2023);

Aortic valve wire injury (AVWI) (Honda et al. 2014; Iqbal et al. 2023; Li et al. 2023; Peng et al. 2022; Toshima et al. 2020; Zhao et al. 2022; Zhong et al. 2023)

Controlled injury; Study of acute responses

Limited relevance to human pathophysiology; Lack of disease progression; Ethical considerations; Limited variability and standardization