H4H · Exploring the therapeutic potential of homoarginine in experimental models of ischemia reperfusion injury and chronic heart failure
FP7 — People (Marie Curie Actions)
- Duration
- 2014-04-01 → 2016-03-31
- EU contribution
- €221,606
- Participants
- 1
- Scheme
- MC-IEF
Lines connect the coordinator with its partners.
Results in brief
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
Data: CORDIS, © European Union
Project objective
Cardiovascular disease (CVD) remains the leading cause of death within the European Union and new, more effective forms of treatment are urgently needed. Recent studies have shown that patients with low plasma homoarginine are at increased risk of stroke, myocardial infarction and heart failure (HF). This project aims to explore the underlying mechanisms of this association and to determine the therapeutic potential of homoarginine supplementation. We have already shown that mice with homoarginine-deficiency exhibit increased brain injury following an experimental stroke, and further, that elevating homoarginine levels is protective in normal mice. We hypothesize that homoarginine is more a mediator than a mere biomarker for positive outcome in CVD. Specifically, we propose that increased homoarginine in mice will also be beneficial in experimental models of acute ischaemia and chronic HF. Our objectives are, 1) to study whether low homoarginine levels are detrimental in the ischaemic and failing heart and demonstrate rescue by homoarginine treatment; 2) to determine whether homoarginine supplementation is beneficial; and 3) to elucidate the mechanism for how homoarginine exerts its cardiac effects. This interdisciplinary project brings together the applicant’s (Germany) specific expertise in pharmacology and detailed knowledge of the homoarginine research field, with the opportunity to receive extensive in vivo training in an array of cutting-edge murine cardiac phenotyping techniques developed by the scientist in charge (UK). For example, LV catheterization, in vivo MRI, echocardiography, 31P-NMR and surgical models of ischaemia and HF in mice. In conclusion, by extensive training of the Fellow, this project will 1) pave the road to develop scientific independence, 2) foster intra-European collaboration, 3) provide a basis for further funding, and 4) give novel insights into CVD pathophysiology to the scientific community and to the general public.
Original text from CORDIS.
Participants
- THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF OXFORD · OxfordCoordinatorUnited Kingdom
Links
Data: CORDIS, © European Union