Rodent Models of Dilated Cardiomyopathy and Heart Failure for Translational Investigations and Therapeutic Discovery

Abstract

Even with modern therapy, patients with heart failure only have a 50% five-year survival rate. To improve the development of new therapeutic strategies, preclinical models of disease are needed to properly emulate the human condition. Determining the most appropriate model represents the first key step for reliable and translatable experimental research. Rodent models of heart failure provide a strategic compromise between human in vivo similarity and the ability to perform a larger number of experiments and explore many therapeutic candidates. We herein review the currently available rodent models of heart failure, summarizing their physiopathological basis, the timeline of the development of ventricular failure, and their specific clinical features. In order to facilitate the future planning of investigations in the field of heart failure, a detailed overview of the advantages and possible drawbacks of each model is provided.

RhoA/ROCK Pathway Is Upregulated in Experimental Autoimmune Myocarditis and Is Inhibited by Simvastatin at the Stage of Myosin Light Chain Phosphorylation

“…Rat heart physiology, contraction patterns, and energetics are similar to those of humans. Rodent and human myocardial tissue is also similar, although rodent cardiomyocytes contain predominantly alpha-myosin heavy chains (compared to beta-myosin heavy chains in humans) which are characterized by rapid ATPase activity, facilitating high heart rates and short cardiac cycles [ 51 ]. The small physical size of rats must also be taken into account because only a limited number of post-mortem analyses can be performed on the same rat due to the small size of the tissues.…”

A Rat Model of Clinically Relevant Extracorporeal Circulation Develops Early Organ Dysfunctions

“…On the other hand, rodent models are less expensive in comparison, allowing an increased range of testing that is still comparable to human physiology, particularly for cardiovascular function. However, there many are deviations from human physiology that need to be understood, such as higher metabolic rates, slightly different cardiac electric activity and structure, and a higher heart rate [ 5 , 6 , 7 ]. The ECC rat models described thus far have made it possible, for example, to study in a reproducible way the weaning of ECC and the impact of anti-coagulants, hypothermia, and cardioplegia, without recovery in most cases [ 8 , 9 , 10 ].…”

A Mouse Model of Dilated Cardiomyopathy Produced by Isoproterenol Acute Exposure Followed by 5-Fluorouracil Administration

“…While for CAD a significant number of therapeutic approaches exist, for DCM, there is a need to develop novel preventative and reparative therapies [ 5 ]. The development of these novel therapies requires testing the putative therapeutic strategies in appropriate DCM animal models [ 6 ].…”

“…Ischemic cardiomyopathy is the most common type of DCM. On the other hand, primary DCM is a non-ischemic heart muscle disease with diverse etiologies, including genetic mutations, infections, inflammation, autoimmune diseases, exposure to toxins and endocrine or neuromuscular causes [ 5 , 6 ]. Idiopathic and familial disease are the most reported causes of primary DCM [ 5 , 6 ].…”

“…On the other hand, primary DCM is a non-ischemic heart muscle disease with diverse etiologies, including genetic mutations, infections, inflammation, autoimmune diseases, exposure to toxins and endocrine or neuromuscular causes [ 5 , 6 ]. Idiopathic and familial disease are the most reported causes of primary DCM [ 5 , 6 ]. Mutations in several genes cause DCM, including genes encoding structural components of the sarcomere and desmosome [ 5 ].…”