NGFN-TRANSFER
Metabolomics in Heart Failure as a Novel Diagnostic Tool
| Coordinator: | Prof. Dr. Hugo A. Katus | |
| Institution: | Abteilung Innere Medizin III, Uniklink Heidelberg | |
| Homepage: | www.klinikum.uni-heidelberg.de |
Due to improved acute care, especially in ischemic heart diseases, chronic heart failure has become the most prevalent cardiovascular disorder in industrialized western countries. On the molecular level, the heart adapts to an increased work load by extensive changes in protein composition, ultimately resulting in deterioration of functional characteristics of the diseased heart muscle (myocardium). Although initiated as myocardial dysfunction, heart failure soon becomes a systemic disorder with neurohormonal activation and reduced blood flow to end organs. This project will be cooperatively performed with the company metanomics in Berlin, which is specialized in metabolomic analysis and bioinformatics.
The aims of the project are to characterize the “metabolome” of the failing heart as reflected by metabolites in blood samples of clinically excellent characterized patient cohorts.
It is expected to identify metabolic signatures that
(i) are diagnostic of myocardial failure
(ii) relate to disease severity and
(iii) may even provide clues to disease mechanisms and affected molecular pathways.
Therefore, two complementary scientific strategies will be devised. First, in carefully phenotyped patients with heart failure, metabolic profiles will be obtained, compared to healthy controls and subsequently related to clinical findings. Secondly, defined animal models with heart failure will be investigated, allowing a comparison of gene expression and metabolomic changes. Taken together, we expect to provide a novel approach for heart failure diagnostics and risk assessment as well as to identify novel pathways for dissection of the molecular and pathomechanistic causes of Heart Failure and for new approaches to develop future therapeutic interventions.
To reach this final goal two complementary scientific approaches will be followed:
(1) Metabolic profiles of clinically well characterized Heart Failure patients will be analyzed and correlated to clinical parameters.
(2) Cardiac gene expression profiles in well defined Heart Failure animal models will be compared to metabolomic profiles.
This combined approach should allow to develop new biomarkers for diagnostics and risk stratification of Heart Failure and to detect new molecular pathomechanisms and new therapeutic approaches..
The aims of the project are to characterize the “metabolome” of the failing heart as reflected by metabolites in blood samples of clinically excellent characterized patient cohorts.
It is expected to identify metabolic signatures that
(i) are diagnostic of myocardial failure
(ii) relate to disease severity and
(iii) may even provide clues to disease mechanisms and affected molecular pathways.
Therefore, two complementary scientific strategies will be devised. First, in carefully phenotyped patients with heart failure, metabolic profiles will be obtained, compared to healthy controls and subsequently related to clinical findings. Secondly, defined animal models with heart failure will be investigated, allowing a comparison of gene expression and metabolomic changes. Taken together, we expect to provide a novel approach for heart failure diagnostics and risk assessment as well as to identify novel pathways for dissection of the molecular and pathomechanistic causes of Heart Failure and for new approaches to develop future therapeutic interventions.
To reach this final goal two complementary scientific approaches will be followed:
(1) Metabolic profiles of clinically well characterized Heart Failure patients will be analyzed and correlated to clinical parameters.
(2) Cardiac gene expression profiles in well defined Heart Failure animal models will be compared to metabolomic profiles.
This combined approach should allow to develop new biomarkers for diagnostics and risk stratification of Heart Failure and to detect new molecular pathomechanisms and new therapeutic approaches..
