Identification of New Biomarkers of Heart Failure by Proteomic Analysis of Plasma Proteins

Coordinating Institution: CRP Sante
Contracting Partner(s): CRP Gabriel Lippmann , Centre Hospitalier de Luxembourg , Institut National de Chirurgie Cardiaque et de Cardiologie Interventionnelle - INCCI (L) , Société Luxembourgeoise de Cardiologie
From: 01/01/2009
To: 31/12/2010
Budget: 495,000.00€
Contact(s): Devaux Yvan

Summary

Heart failure (HF) following myocardial infarction (MI) represents a major disease burden in modern countries, both in terms of financial cost, mortality and morbidity. It is a main public health problem and has become the leading cause of death in Luxembourg. Beside the search for new treatments of HF, our activity focuses on the search for new prognostic biomarkers of HF. Identification of patients at risk of developing HF after MI is indeed one of our research priorities since HF is potentially preventable. In the last few years, research in the biomarker field has highly benefited from the rapid development of high-throughput technologies such as “omics”-based technologies. Taking profit from the national registry of infarction, which accounts now over 500 patients, we performed a transcriptomic analysis to identify biomarkers of HF. Bioinformatic analyses combining transcriptomic data with networks of protein-protein interactions emphasized a few potential new biomarkers. Persuaded that the development of HF is a complex phenomenon that has to be assessed with the concepts of systems biology, we intended to couple our transcriptomic approach with proteomic analysis of plasma proteins. Through a collaboration with the Department Environment and Agro-biotechnologies of the CRP-Gabriel Lippmann, we are now in the process of generating blood-based biosignatures using proteomic analysis of plasma proteins from MI patients. The first steps of this project involved the implementation of the procedure. Following preliminary tests revealing a significant rate of protein degradation during sampling and storage, we have chosen P100 tubes for plasma collection in order to minimize protein degradation. Since highly abundant plasma proteins prevent the detection of less abundant proteins on two dimensional gels, and considering that biomarkers are often in low concentration in the plasma, we implemented a technique to deplete plasma from two highly abundant proteins, immunoglobulins G and serum albumin. These accomplishments allowed us to generate gels that can be used to determine which proteins are disproportionately expressed in patients with HF compared with patients who did not develop HF. We are now in the process of selecting two groups of MI patients that will be used for following analyses.