Growth factor therapy to prevent postinfarction heart failure

[Speaker] Kai C. Wollert:1
1:Department of Cardiology and Angiology, Division of Molecular and Translational Cardiology, Hannover Medical School, Germany

Improved reperfusion strategies have shortened ischemic times and enhanced myocardial salvage in most patients with acute myocardial infarction (MI). Despite these achievements, patients with extensive myocardial injury during the acute phase remain at risk of developing chronic heart failure. MI triggers an inflammatory response that replaces the necrotic area with vascularized granulation tissue and eventually a collagen-rich scar. The heart can undergo deleterious changes in left ventricular geometry and function during this vulnerable period before scar formation has stabilized the infarct area. Therapeutic modulation of infarct healing may therefore hold promise for preventing postinfarction heart failure. Intracoronary infusion of autologous bone marrow cells (BMCs) during this critical time window has been explored as an adjunctive therapeutic strategy to improve heart function after MI in patients. Transcriptome and proteome analyses indicate that various BMC populations release a broad repertoire of cytokines and growth factors that may enhance tissue repair in a paracrine manner, thus providing a conceptual framework for this approach. However, BMC therapy is limited by low cell retention rates after intracoronary or intramyocardial delivery and by interindividual variations in cell functionality. We believe that systemic application of specific BMC-derived secreted proteins will enable more targeted approaches to improving tissue repair and heart function after MI. We recently performed a bioinformatic secretome analysis in BMCs from patients with acute MI who were enrolled in the BOOST 2 cell therapy trial. From this analysis, we identified several poorly characterized angiogenic growth factors. The mode of action and therapeutic potential of these proteins will be discussed during my talk.
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