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Exploring the therapeutic potential of homoarginine in experimental models of ischemia reperfusion injury and chronic heart failure

Final Report Summary - H4H (Exploring the therapeutic potential of homoarginine in experimental models of ischemia reperfusion injury and chronic heart failure)

Diseases of the heart and circulatory system (cardiovascular disease, CVD) are the main cause of death in Europe. According to the European Society of Cardiology, each year CVD causes over 4 million deaths in Europe (47 % of all deaths). The main forms of CVD are stroke and coronary heart disease (CHD), a condition where insufficient blood reaches the heart muscle due to atherosclerotic narrowing of the arteries. This manifests as angina or life-threatening myocardial infarction (MI), conditions which, over time, may lead to heart failure (HF). Recent studies have shown that patients with low plasma concentrations of the endogenous amino acid homoarginine are at increased risk of stroke, MI and HF. This Marie Curie project “Homoarginine for Heart (H4H)” aimed to investigate the involvement of the homoarginine-pathway, in order to advance our knowledge in terms of risk-stratification, prevention, and novel treatment strategies for CVD.
During her Fellowship, the Fellow has generated a substantial amount of data following the project hypothesis. The Fellow received extensive training and transferable skills in experimental models of HF, in vivo imaging and LV catheterization. Along with this, the Fellow was trained in single cell experiments in order to study calcium-handling in cardiomyocytes. For mechanistic studies, the Fellow furthermore performed a broad range of cutting edge biochemical assays such as the biotin switch assay and NOS activity assay as well as NO bioavailability, biopterin and superoxide quantification measurements.
This interdisciplinary project brought together the Fellow’s (Germany) specific expertise in pharmacology and detailed knowledge of the homoarginine research field with the unique opportunity to receive extensive in vivo training in an array of cutting-edge murine cardiac phenotyping techniques developed by the scientist in charge and collaborators on-site (Oxford, UK). In conclusion this project 1) paved the road to develop scientific independence for the Fellow, 2) fostered intra-European collaboration, 3) provided a basis for further funding, and 4) provided novel insights into CVD pathophysiology including potential therapeutic options to the scientific community and to the general public.

Contact details:
Dr. Dorothee Atzler, email: dorothee.atzler@gmail.com
or
Prof. Craig Lygate, email: clygate@well.ox.ac.uk

Website: http://www.rdm.ox.ac.uk/principal-investigators/researcher/craig-lygate