Cardiac Hypertrophy and Heart Failure Models

Cardiac hypertrophy, the enlargement of the heart muscle in response to increased workload, is a key adaptive response that may progress to maladaptive remodelling and heart failure. Heart failure arises when the myocardium can no longer sustain sufficient cardiac output to meet metabolic demands, leading to symptomatic congestion and organ hypoperfusion. Preclinical models are indispensable for elucidating the mechanisms that drive the transition from compensated hypertrophy to decompensated failure and for testing novel therapies. Pressure-overload paradigms, most notably transverse aortic constriction (TAC) and aortic banding in rodents, recapitulate the pathological sequence of concentric hypertrophy, fibrosis, ventricular dilation and systolic or diastolic dysfunction. Variations in the degree and location of constriction, species, strain and sex yield diverse phenotypes, allowing investigators to model preserved or reduced ejection fraction, biventricular remodelling and secondary pulmonary hypertension. Complementary models of volume overload, myocardial infarction and genetic manipulation further expand the toolkit, each capturing distinct aspects of the human clinical spectrum. Advanced imaging, molecular profiling and functional assays enhance the translational value of these models. Collectively, the repertoire of experimental systems provides critical insight into the interplay between biomechanical stress, neurohormonal activation, cellular signalling and extracellular matrix remodelling that underpins cardiac disease progression.

Research from Nature Portfolio

Recent studies have delineated how discrete degrees of pressure overload produce graded patterns of hypertrophy and failure. In mice subjected to varying gauges of transverse aortic constriction, distinct phenotypes emerged: mild constriction induced compensatory concentric remodelling, whereas tighter constriction drove systolic dysfunction, fibrosis and biomarkers of heart failure. Parallel work in rat models of aortic banding has uncovered unique microRNA signatures associated with the rapid transition from hypertrophy to overt failure. Specific microRNAs were shown to orchestrate post-transcriptional repression of genes governing cytoskeletal integrity, angiogenesis and stress response, pinpointing regulatory nodes that distinguish adaptive from maladaptive hypertrophic growth.

Cardiac Hypertrophy and Heart Failure Models publication trend

The graph below shows the total number of articles in cardiac hypertrophy and heart failure models across all publications each year (not limited to Nature Index journals).

Technical terms

Cardiac hypertrophy: Enlargement of heart muscle cells with increased wall thickness in response to elevated workload.

Heart failure: A syndrome in which the heart cannot pump sufficient blood to meet the body’s needs, often with congestion and reduced exercise tolerance.

Pressure overload: Increased afterload on the ventricle, typically induced by arterial constriction, leading to hypertrophic remodelling.

Transverse aortic constriction (TAC): A surgical procedure in rodents that narrows the aorta to simulate chronic hypertension and pressure overload.

Ejection fraction: The percentage of blood ejected from a ventricle during systole, used as a measure of contractile function.

Cardiomyocyte: A specialised heart muscle cell responsible for contraction and force generation.

References

1. Distinct Phenotypes Induced by Three Degrees of Transverse Aortic Constriction in Mice. Scientific Reports (2019).
2. Pressure overload-induced systolic heart failure is associated with characteristic myocardial microRNA expression signature and post-transcriptional gene regulation in male rats. Scientific Reports (2023).
3. Rodent Models of Dilated Cardiomyopathy and Heart Failure for Translational Investigations and Therapeutic Discovery. International Journal of Molecular Sciences (2023).
4. Differential mRNA Expression and Circular RNA-Based Competitive Endogenous RNA Networks in the Three Stages of Heart Failure in Transverse Aortic Constriction Mice. Frontiers in Physiology (2022).