**Sarat Chandra Yenisetti** Nagaland University, India

**1**

**Chapter 1**

**Abstract**

Animal Models of

Cardiomyopathies

Cardiomyopathies are a heterogeneous group of disorders of heart muscle that ultimately result in congestive heart failure (CHF). Rapid progress in genetics as well as in molecular and cellular biology over the past three decades has greatly improved the understanding of pathogenic signaling pathways in inherited cardiomyopathies. This chapter will focus on animal models of different clinical forms of human cardiomyopathies with their summaries of triggered key molecules, and

*Enkhsaikhan Purevjav*

signaling pathways will be described.

**Keywords:** cardiomyopathy, heart failure, genetic mutation

**1. From genetic abnormality to cardiomyopathy phenotype**

It's widely accepted that inherited cardiomyopathies are a group of heterogeneous diseases of heart muscle resulting from genetic alterations in cardiac myocytes, the chief contractile cell type in the heart [1]. The genes encoding proteins that build muscle cytoskeleton and contractile apparatus are responsible for a cardiomyopathy phenotype with distinctive morpho-/histological cardiac remodeling [2]. Further, disruption of particular genetic and protein networks and pathways may intersect with other intracellular and intercellular pathways and disturbances in molecular signaling. Apoptosis, necrosis, autophagy, and metabolic and arrhythmogenic fluxes—which may present as the sole features or as overlapping signs of decompensated cardiac homeostasis—result in definitive forms of cardiac remodeling including fibrosis, cardiomyocyte hypertrophy, and atrophy. Typically, molecular signaling activates associated compensatory responses and cooperates with other modifiers such as genetic modifiers and environment, stress, or toxicity related that, in turn, may or may not influence the final cardiomyopathy phenotype. Alterations in cellular morphology and size, gene expression patterns, and metabolic shifts in cardiomyocytes initially compensate and maintain cardiac function in the subtle, preclinical stages of cardiomyopathy. Thus, inherited forms of cardiomyopathy, irrespective of the specific genetic or morpho-/clinical condition, may or may not present signs of a failing heart. Five types of inherited cardiomyopathies are distinguished based on clinical features: dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy (HCM), restrictive cardiomyopathy (RCM), arrhythmogenic ventricular cardiomyopathies (ACM), and left ventricular noncompaction cardiomyopathy (LVNC) [3] as demonstrated in **Table 1**. DCM is characterized by left ventricular (LV) dilation and systolic dysfunction; HCM is characterized by LV hypertrophy with diastolic dysfunction; and RCM is accompanied by increased stiffness of the myocardium and dilated atria due to
