Heart failure and mouse models

Abstract

Heart failure is a common, complex condition with a poor prognosis and increasing incidence. The syndrome of heart failure comprises changes in electrophysiology, contraction and energy metabolism. This complexity, and the interaction of the clinical syndrome with very frequently concurrent medical conditions such as diabetes, means that animal modelling of heart failure is difficult. The current animal models of heart failure in common use do not address several important clinical problems. There have been major recent advances in the understanding of cardiac biology in the healthy and failing myocardium, but these are, as yet, unmatched by advances in therapeutics. Arguably, the development of new animal models of heart failure, or at least adaptation of existing models, will be necessary to fully translate scientific advances in this area into new drugs. This review outlines the mouse models of heart failure in common usage today, and discusses how adaptations in these models may allow easier translation of animal experimentation into the clinical arena.

Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunction without affecting blood pressure in angiotensin II-high salt-induced hypertension

“…Whereas heart dysfunction is one important complication of hypertension in humans, Ang II-infused, hypertensive mice have little cardiac dysfunction. In fact, there are no mouse models of heart failure induced by systemic hypertension [20,21]. In the present study, we used a mouse model of Ang II-induced hypertension combined with a high-salt diet (4% NaCl in the chow).…”

Selection of reference genes for normalization of real-time PCR data in minipig heart failure model and evaluation of TNF-α mRNA expression

“…Nevertheless, the need to translate experimental results into medical applications made the use of larger animal models inescapable. At present, the pig is the most eligible experimental animal model for studying cardiovascular disease and is especially used in studies on heart failure (HF) (Bader, 2010;Breckenridge, 2010;Dixon and Spinale, 2009;Recchia and Lionetti, 2007). HF is the final common pathway of most primary cardiovascular diseases, and involves several anatomic, microstructural, functional alterations including numerous molecular and cellular events (Mann, 1999).…”

“…HF is the final common pathway of most primary cardiovascular diseases, and involves several anatomic, microstructural, functional alterations including numerous molecular and cellular events (Mann, 1999). To date, the pacing-induced HF model is considered the gold standard in HF experimental research and offers undeniable advantages with respect to other models for its relative simplicity, reproducibility, and similarities with many features of clinical dilated cardiomyopathy (Helmer et al, 1996;Breckenridge, 2010).…”

Guidelines for Translational Research in Heart Failure

“…Their use has advanced our knowledge of adaptive and maladaptive remodeling and, in the process, has unveiled the molecular mechanisms underlying these responses as rational drug targets [16]. A recent statement paper extensively described some of the models used in HF research [17].…”