Heart failure (HF) is a condition that affects the pumping ability of the heart, progressively reducing cardiac output and leading to inadequate blood flow. Heart failure can thus impact on peripheral tissues such as the liver, in which a unique form of liver injury and severe cirrhosis can occur, called cardiac hepatopathy (CH). With HF becoming increasingly prevalent, so too are the number of patients presenting with CH, impacting clinical management strategies. Whilst poor cardiac output and reduced blood circulation are related to development of CH, there is still very little known about the timeline and underlying molecular mechanisms, due in part to the lack of relevant preclinical models.
We have developed a new, genetically inducible mouse model of HF driven by cardiomyocyte specific mitochondrial dysfunction, which leads to unique activation of cellular stress responses in the heart. In preliminary studies, we have shown that this model presents with classic complications of chronic heart failure at approximately 30 weeks after genetic induction, characterised by congestive heart failure, rapid weight loss, and eventual death. Unexpectedly however, this model also displays significant cardiac hepatopathy, which is not a common feature observed in other heart failure models (TAC/MI/Mst1-tg). Thus, this model places us in an advantageous position to make major inroads into our understanding of the mechanisms driving HF, and subsequent comorbidities such as cardiac hepatopathy. These studies will include the use of TurboID technology, which allows for the identification of proteins secreted specifically by the heart into circulation, providing unprecedented insights into the blood borne factors released by the failing heart that drive disease.
We will use male and female mice with heart specific induction of mitochondrial dysfunction to investigate the progressive timeline and underlying mechanisms of these pathologies.
Last updated20 October 2025