Abstract 20780: Cardiac Progenitor Cell's Secretome in Health and Heart Failure

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Abstract

Introduction: The cellular microenvironment of cardiac progenitor cells plays a crucial role in the maintenance of heart function and the regeneration of damaged myocardium.

Hypothesis: We aimed to explore the autocrine control of resident Sca-1+ progenitor cells in response to pathological conditions such as heart failure. In addition, we evaluated the functional significance of exposing these cells to healthy versus diseased cellular microenvironment, with a special focus on their angiogenesis and proliferation potential.

Methods: Conditioned media was generated for 24 h from stem cell antigen-1 (Sca-1+) progenitor cells that were isolated from hearts of wild type (Wt) and transgenic heart failure mice featuring an αMHC-cyclin-T1/Gαq overexpression (Cyc). Global secretome profiling was performed via label-free mass spectrometric quantification.

Results: Sca-1+ cells released a wide array of cardioprotective growth factors and cytokines such as IGF1, MYDGF, VEGFD, TGFß2, CSF1 and CCL7 into the medium under healthy conditions. Notably, in the heart failure milieu, ECM proteins like fibronectin, biglycan, versican and angiogenic regulators such as VEGFD, angiopoietin-2, PAI1 were higher abundant (> 2-fold) than under healthy condition. Pathway analysis of differentially enriched factors under disease condition revealed an association with angiogenesis, cell proliferation and cell movement functions. Furthermore, we evaluated the influence of soluble factors that were identified in the secretome of Sca-1+ on angiogenesis in vitro, which was assessed via tubule formation. After exposing Sca-1+ cells for 24 h to a diseased cellular environment, tube formation was significantly induced in Cyc cells by 3-fold when compared to Wt cells. Conversely, the proliferation of Wt cells was improved by 2-fold but only (~1.3 fold) in Cyc cells under similar conditions.

Conclusions: Our findings revealed that Sca-1+ cells release several cardioprotective factors under heart failure conditions, which might function in an autocrine manner to stimulate angiogenesis and proliferation known to be critical for cardiac repair and regeneration

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