February 2014

Targeting Cardiac Fibrosis for Heart Failure Treatment

Mon, 10 February 14 12:40

Three UCD clinical researchers have secured a third FP7 research award which aims to investigate cardiac fibrosis in the treatment of heart failure.  The researchers, Professor Ken McDonald (UCD Associate Clinical Professor), Dr Mark Ledwidge, and Dr Chris Watson (UCD Post-doctoral fellow) build on previous European collaborative efforts with the FIBRO-TARGETS project.

Bringing together eleven European partners in six different countries from public research organisations and industry, FIBRO-TARGETS aim to target cardiac fibrosis for heart failure treatment.

Specifically, the consortium will focus on clarifying the mechanisms involved in myocardial interstitial fibrosis (MIF) that contributes to heart failure and are likely to become therapeutic targets for this disease.

MIF is one of the key mechanisms of cardiac remodelling. It results from the excessive accumulation and modifications of the properties of proteins that make up the extracellular matrix.

Cardiac fibrosis contributes to cardiac tissue stiffness. This adversely impacts the normal functioning of the heart and, over time, causes symptomatic heart failure with symptoms of breathlessness, congestion, oedema and fatigue.

More than 6.5 million people suffer from heart failure in Europe. The incidence is increasing at an alarming rate because of an aging population and the outbreak of cardiovascular risk factors such as diabetes, obesity and high blood pressure. This serious, often irreversible, disease is the leading cause of hospitalisation for patients over the age of 65.

Early interventions targeting key mechanisms, including myocardial interstitial fibrosis, could slow down progression to and worsening of heart failure. The FIBRO-TARGETS project proposes an innovative approach to detect cardiac abnormalities early using circulating biomarkers of myocardial interstitial fibrosis.

The initial objective for the consortium is to confirm the main biological mechanisms involved in myocardial interstitial fibrosis. They hope to experimentally validate new molecules and targeted therapeutic strategies that improve the quality of the cellular matrix and limit myocardial interstitial fibrosis. Finally, these targets could be used as biomarkers to predict, monitor and describe the response to myocardial interstitial fibrosis treatments.

Dr Chris Watson (SMMS Postdoctoral Fellow at UCD Conway Institute) said,

“Our research contribution to the project will involve heart failure phenotyping using a biomarker based approach (protein and miRNA) and monitoring changes in these novel MIF biotargets in response to anti-fibrotic therapy. Some of this work will be carried out in our STOP-HF patient population, a recently described novel longitudinal cohort with cardiovascular disease risk factors that has captured new onset heart failure progression in real time (Ledwidge et. al. JAMA 2013). We are excited to be involved in FIBRO-TARGETS as it builds on our current research investigating novel biomarkers and therapies for heart failure."

This is the third FP7 project on heart failure that this UCD team are involved in.

HOMAGE (Heart OMics in AGEing) launched in February 2013 aims to validate specific biomarkers of heart failure and MEDIA (MEtabolic Road to DIAstolic Heart Failure) is investigating mechanisms, biomarkers and therapies for metabolic disease driven diastolic heart failure. Collectively, these three FP7 project awards to Professor Ken McDonald, Dr Mark Ledwidge, and Dr Chris Watson amount to 1.8 million euro of funding to UCD.