A new animal model of heart disease with various risk factors to more accurately evaluate therapies

Professor Andrew Murphy, The University of Melbourne

Vanguard Grant - 2 Year

Years funded: 2025 - 2026

A new model to improve heart disease therapies

It is all too often that therapies fail in cardiovascular clinical trials. This is an expensive exercise and the reasons for this are many. One of the major discrepancies is that discovery science (preclinical) is often done in mouse models with one major risk-factor, which is certainly not the clinical scenario. While preclinical models allow us to dissect the organ of interest and explore questions that are unable to be answered in clinical studies, the models used are not outcomes studies where either death or a major adverse cardiovascular event (MACE) is seen.

Introducing multiple cardiovascular and metabolic risk factors

We propose to evolve a model where we can use traditional and new models of atherosclerosis in a setting of cardiac directed hypertension that develop atherosclerotic plaques in the coronary arteries that eventually rupture, occlude and cause myocardial infarctions. We will evolve this model by adding on risk factors such as varying levels of cholesterol, obesity, insulin resistance, diabetes, inflammatory high salt diets. This will give a more accurate depiction of the individuals that many future therapies will target. We will characterise these mice and determine a range of parameters (functional & biochemical) over time until the endpoint (MACE) / survival.

Testing therapies and safety through targeted intervention

Once this is characterized and established, we will provide proof of concept drug screen by blocking one of the proteins we have found to be increased across many of these risk factors and where blocking has provided a reduction in atherosclerosis. Further, this model will help with safety studies, an important part of drug discovery and development.