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Cardiac matrix modulation after myocardial infarction

Dr Tejas Deshmukh, Institution: University of Sydney

2020 Health Professional Scholarship

Years funded: 2021-2023


Cardiovascular disease is a leading cause of death in Australia, with myocardial infarction (MI) and ischaemic heart disease being the major culprits. Although revascularisation (artery-opening) strategies over the last 3 decades have had a significant impact on early mortality, incremental benefits have plateaued. For these reasons, morbidity from chronic heart failure (HF) is increasing. The current treatment paradigm is to slow adverse cardiac remodelling (chronic HF stage) and to treat end-stage HF with heart transplantation. This is not a long-term solution. If we can shift the treatment paradigm towards regenerating injured tissue and fundamentally changing the cardiac scar that results after injury (coupled with quality measures for preventative care) enormous health care cost savings and decreased morbidity and mortality will result.

We have previously shown that recombinant human Platelet Derived Growth Factor (rhPDGF) can improve the heart function of both mice and pigs after induced heart attack. Before this promising therapy can be considered for clinical trials, further mechanistic details need to be elucidated. This will impact both early phase clinical trial design and be hypothesis generating for future regenerative therapies. The first part of the project will investigate the molecular and cellular changes that rhPDGF has on the infarcted heart. This will use novel and cutting-edge tools including high dimensional flow cytometry, mass cytometry and tensor diffusion imaging on cardiac MRI. The second part focuses on detailing the impact of scar homogeneity (by rhPDGF) on cardiac conduction, re-entrant circuits and ventricular arrhythmias. Outcomes of this project include expedited progression of this promising therapy, from the laboratory into the clinic where thousands of heart failure patients could one day benefit.

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