Examining the role of mitochondrial oxidative stress in dilated cardiomyopathy using a novel therapeutic probe

Dilated cardiomyopathy (DCM) is a common cause of heart failure and the most common indication for heart transplantation.

Oxidative stress appears to be a key driver of disease progression, leading to mitochondrial dysfunction, contractile impairment, myocyte hypertrophy and interstitial fibrosis. Specifically targeting mitochondrial-generated oxidative stress appears crucial to modifying the disease course.

Mitoquinone is a mitochondrial-targeted antioxidant that reduces adverse remodelling and improves mitochondrial function in animal models of heart failure. It also reduces markers of oxidative stress in older adults.

By reducing mitochondrial oxidative stress in patients with DCM, it may improve myocardial energetics and contractile function, reduce myocyte hypertrophy and fibrosis and improve the adverse metabolic signature of heart failure.

In this fellowship, I will explore the effects of reducing mitochondrial oxidative stress in patients with DCM in a randomised controlled trial of mitoquinone.

I will utilise advanced cardiovascular magnetic resonance techniques and high-throughput metabolomics to examine the effect on cardiac and skeletal muscle energetics, myocyte hypertrophy and fibrosis, myocardial function and systemic metabolic dysfunction.

Building on my current skills, I will develop expertise in magnetic resonance spectroscopy, metabolomics and clinical trials to become a leading scientist investigating cardiac metabolism and novel therapies for cardiomyopathy using advanced imaging.