*2.2.4 Arrhythmogenic ventricular cardiomyopathy models*

Many models of ARVC with mutations in genes encoding desmosomal (DSP, PKP, DSC, DSG, and JUP) and non-desmosomal (RYR2, TMEM43, and ZASP) proteins have been developed [118]. Structural and functional alterations include progressive, diffuse, or segmental loss of cardiomyocytes, probably due to cardiomyocyte apoptosis or necrosis, and replacement with fibrotic and adipose tissue (**Table 4**). Fibro-fatty tissue primarily is seen in the right ventricle (RV), with common LV involvement in later stages of the disease [119] (**Table 5**).

#### *2.2.5 Left ventricular noncompaction cardiomyopathy models*

Animal models of LVNC typically demonstrate a spongiform ventricular myocardium and deep trabeculations, and many reports suggested that LV trabeculation and compaction processes are two distinct but tightly interconnected morphogenetic events resulting in the development of a functionally proficient ventricular chamber wall [140]. Animal models exhibiting LVNC phenotypes and potential pathogenetic mechanisms are summarized in **Table 6**.

## **3. Conclusion**

Advances in molecular and genetic techniques have vastly improved the understanding of molecular mechanisms responsible for cardiomyopathies and cardiac

**9**

**Author details**

Enkhsaikhan Purevjav

Science Center, Memphis, TN, USA

provided the original work is properly cited.

\*Address all correspondence to: epurevja@uthsc.edu

*Animal Models of Cardiomyopathies*

*DOI: http://dx.doi.org/10.5772/intechopen.89033*

dysfunction. The wide range of innovative technologies and techniques used in animal models in vivo has led to advances in our knowledge on the etiology, pathophysiology, and therapeutics of inherited cardiomyopathies. It is clear that mutant proteins in cardiomyocytes can perturb cardiac function whether the prime distress occurs in the contractile apparatus or neighboring cellular complexes, yet persistent cellular stress leads to tissue-, organ-, and organism-level pathology and pathophysiology. However, development and investigation of animal models are complex processes and the outcomes of which could be difficult to translate to humans due to differences in human and animal cardiovascular anatomy and physiology as well as differing pathophysiology of human cardiomyopathies and experimentally induced diseases in animals [160]. Therefore, the choice of appropriate animal model(s) for cardiomyopathy research should utterly rely on clinical knowledge of human cardiovascular diseases, proper research questions, sufficient number of study animals, and correct and relevant interpretation of results and outcomes in animals to human population. Although animal models of human cardiomyopathies often represent incomplete or inaccurate pathological and pathophysiological features seen in humans, the use of animal models not only has improved our knowledge on the etiology and mechanisms of cardiac muscle diseases and therapeutic interventions but also has greatly promoted an advancement in cardiac tissue engineering, induced pluripotent stem cells (iPSCs) technology, in silico and in vitro techniques,

and preclinical assessment of drug discovery and development [161].

Department of Pediatrics, The Heart Institute, University of Tennessee Health

© 2019 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/ by/3.0), which permits unrestricted use, distribution, and reproduction in any medium,

## *Animal Models of Cardiomyopathies DOI: http://dx.doi.org/10.5772/intechopen.89033*

*Animal Models in Medicine and Biology*

*2.2.4 Arrhythmogenic ventricular cardiomyopathy models*

*Animal models of left ventricular noncompaction cardiomyopathy [141–159].*

Many models of ARVC with mutations in genes encoding desmosomal (DSP, PKP, DSC, DSG, and JUP) and non-desmosomal (RYR2, TMEM43, and ZASP) proteins have been developed [118]. Structural and functional alterations include progressive, diffuse, or segmental loss of cardiomyocytes, probably due to cardiomyocyte apoptosis or necrosis, and replacement with fibrotic and adipose tissue (**Table 4**). Fibro-fatty tissue primarily is seen in the right ventricle (RV), with

Animal models of LVNC typically demonstrate a spongiform ventricular myocardium and deep trabeculations, and many reports suggested that LV trabeculation and compaction processes are two distinct but tightly interconnected morphogenetic events resulting in the development of a functionally proficient ventricular chamber wall [140]. Animal models exhibiting LVNC phenotypes and potential

Advances in molecular and genetic techniques have vastly improved the understanding of molecular mechanisms responsible for cardiomyopathies and cardiac

common LV involvement in later stages of the disease [119] (**Table 5**).

*2.2.5 Left ventricular noncompaction cardiomyopathy models*

pathogenetic mechanisms are summarized in **Table 6**.

**8**

**3. Conclusion**

**Table 6.**

dysfunction. The wide range of innovative technologies and techniques used in animal models in vivo has led to advances in our knowledge on the etiology, pathophysiology, and therapeutics of inherited cardiomyopathies. It is clear that mutant proteins in cardiomyocytes can perturb cardiac function whether the prime distress occurs in the contractile apparatus or neighboring cellular complexes, yet persistent cellular stress leads to tissue-, organ-, and organism-level pathology and pathophysiology. However, development and investigation of animal models are complex processes and the outcomes of which could be difficult to translate to humans due to differences in human and animal cardiovascular anatomy and physiology as well as differing pathophysiology of human cardiomyopathies and experimentally induced diseases in animals [160]. Therefore, the choice of appropriate animal model(s) for cardiomyopathy research should utterly rely on clinical knowledge of human cardiovascular diseases, proper research questions, sufficient number of study animals, and correct and relevant interpretation of results and outcomes in animals to human population. Although animal models of human cardiomyopathies often represent incomplete or inaccurate pathological and pathophysiological features seen in humans, the use of animal models not only has improved our knowledge on the etiology and mechanisms of cardiac muscle diseases and therapeutic interventions but also has greatly promoted an advancement in cardiac tissue engineering, induced pluripotent stem cells (iPSCs) technology, in silico and in vitro techniques, and preclinical assessment of drug discovery and development [161].
