Relevance of mouse models of cardiac fibrosis and hypertrophy in cardiac research

Abstract

Heart disease causing cardiac cell death due to ischemia–reperfusion injury is a major cause of morbidity and mortality in the United States. Coronary heart disease and cardiomyopathies are the major cause for congestive heart failure, and thrombosis of the coronary arteries is the most common cause of myocardial infarction. Cardiac injury is followed by post-injury cardiac remodeling or fibrosis. Cardiac fibrosis is characterized by net accumulation of extracellular matrix proteins in the cardiac inter-stitium and results in both systolic and diastolic dysfunctions. It has been suggested by both experimental and clinical evidence that fibrotic changes in the heart are reversible. Hence, it is vital to understand the mechanism involved in the initiation, progression, and resolution of cardiac fibrosis to design anti-fibrotic treatment modalities. Animal models are of great importance for cardiovascular research studies. With the developing research field, the choice of selecting an animal model for the proposed research study is crucial for its outcome and translational purpose. Compared to large animal models for cardiac research, the mouse model is preferred by many investigators because of genetic manipulations and easier handling. This critical review is focused to provide insight to young researchers about the various mouse models, advantages and disadvantages, and their use in research pertaining to cardiac fibrosis and hypertrophy.

Effects of bisphenol A on incidence and severity of cardiac lesions in the NCTR-Sprague-Dawley rat: A CLARITY-BPA study

“…The pathology associated with the majority of these effects became most evident following adverse cardiovascular events such as cardiac ischemia or myocardial infarction (17, 19). It is well accepted that experimental interventions resulting in increased β-adrenergic stress, ischemic injury or genetic manipulations are often necessary to reveal cardiac fibrosis and hypertrophy or phenotypes indicative of overt cardiac pathology in rodent models (61). Such manipulations were not possible in this study and only post mortem tissues were available for analysis.…”

Imatinib attenuates cardiac fibrosis by inhibiting platelet-derived growth factor receptors activation in isoproterenol induced model

“…Many animal models have been used for the research of cardiac fibrosis, such as spontaneously hypertensive induced cardiac fibrosis model [18], the surgery models (myocardial infarction model, myocardial ischemia/reperfusion injury model, and transverse aortic constriction model) [45], and the induced models (desoxycorticosterone induced salt-sensitive hypertensive model [19], Ang II induced cardiac fibrosis model [46], and ISO induced cardiac fibrosis model [10]). However, the mechanisms of cardiac fibrosis in different models are diverse.…”

CLARITY‐BPA academic laboratory studies identify consistent low‐dose Bisphenol A effects on multiple organ systems

“…The lack of overt morphology phenotypes in the CLARITY‐BPA or EE exposed hearts was not surprising since pathology associated with the majority of cardiac insults typically becomes evident only after adverse cardiovascular events such as cardiac ischaemia or myocardial infarction . For experimental studies with rodents, it is well‐accepted that an intervention resulting in increased β‐adrenergic stress, ischaemic injury or genetic manipulations are necessary to reveal cardiac fibrosis, hypertrophy or phenotypes indicative of overt cardiac pathology . Such manipulations were not possible in the CLARITY‐BPA study and limit any interpretations resulting from negative data.…”