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During mammalian development, cardiac specification and ultimately lineage commitment to a specific cardiac cell type is accomplished by the action of specific transcription factors (TFs) and their meticulous control on an epigenetic level. In this review, we detail how cardiacspecific TFs function in concert with nucleosome remodeling and histone-modifying enzymes to regulate a diverse network of genes required for processes such as cell growth and proliferation, or epithelial to mesenchymal transition (EMT), for instance. We provide examples of how several cardiac TFs, such as Nkx2.5, WHSC1, Tbx5, and Tbx1, which are associated with developmental and congenital heart defects, are required for the recruitment of histone modifiers, such as Jarid2, p300, and Ash2l, and components of ATP-dependent remodeling enzymes like Brg1, Baf60c, and Baf180. Binding of these TFs to their respective sites at cardiac genes coincides with a distinct pattern of histone marks, indicating that the precise regulation of cardiac gene networks is orchestrated by interactions between TFs and epigenetic modifiers. Furthermore, we speculate that an epigenetic signature, comprised of TF occupancy, histone modifications, and overall chromatin organization, is an underlying mechanism that governs cardiac morphogenesis and disease.

In summary, PTH is a DPP-IV inhibitor leading to an increased cardiac SDF-1 level, which enhances recruitment of CXCR4(+) BMCs into the ischaemic heart associated with attenuated ischaemic cardiomyopathy. Since PTH is already clinically used our findings may have direct impact on the initiation of studies in patients with ischaemic disorders.

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Erythropoietin (EPO) was shown to have protective effects after myocardial infarction (MI) by neovascularization and antiapoptotic mechanisms. Beside direct receptor-dependent mechanisms, mobilization and homing of bone marrow-derived cells (BMCs) may play a pivotal role in this regard. In this study, we intended to track different subpopulations of BMCs and to assess serially myocardial perfusion changes in EPO-treated mice after MI. To allow tracking of BMCs, we used a chimeric mouse model. Therefore, mice (C57BL/6J) were sublethally irradiated, and bone marrow (BM) from green fluorescent protein transgenic mice was transplanted. Ten weeks later coronary artery ligation was performed to induce MI. EPO was injected for 3 days with a total dose of 5000 IU/kg. Subpopulations (CD31, c-kit, CXCR-4 and Sca-1) of EGFP+ cells were studied in peripheral blood, bone marrow and hearts by flow cytometry. Myocardial perfusion was serially investigated in vivo by pinhole single-photon emission computed tomography (SPECT) at days 6 and 30 after MI. EPO-treated animals revealed an enhanced mobilization of BMCs into peripheral blood. The numbers of these cells in BM remained unchanged. Homing of all BMCs subpopulations to the ischaemic myocardium was significantly increased in EPO-treated mice. Among the investigated subpopulations, EPO predominantly affected migration of CXCR-4+ (4.3-fold increase). Repetitively SPECT analyses revealed a reduction of perfusion defects after EPO treatment over time. Our study shows that EPO treatment after MI enhances the migration capacity of BMCs into ischaemic tissue, which may attribute to an improved perfusion and reduced size of infarction, respectively.