Fig. 6

Cardiac DPP4 controls a set of cell proliferation related genes in whole blood. a A network visualization of a subset of genes in either whole blood (left panel) or heart (right panel) that are co-correlating with heart DPP4. Central nodes reflect the names of the top scoring canonical pathways (full list in Additional file 9) with the associated nodes being the genes co-correlating with heart DPP4 that are found in those pathways. Heart DPP4 is in general negatively correlated with nodes in the whole blood cross-tissue network. b Heat map displaying the enrichment scores obtained from gene enrichment profiler (http://xavierlab2.mgh.harvard.edu/EnrichmentProfiler/enrichmentMaps.html) for the whole blood geneset that correlated with heart DPP4 levels. Only a subset of 126 tissues are annotated (for full results see Additional file 10). c A scatter plot of expression levels of CXCR7 versus DPP4 in the heart (correlation coefficient r = 0.224, p value = 0.02). Full enrichment analyses are summarized in Additional file 11. d Literature-based and network-supported associations between DPP4 and SDF-1 with respect to blood and heart. Network-proposed insights are highlighted in blue. The SDF-1/CXCR4 axis has been shown to be critical in tissue repair, including in the heart, as SDF-1 is well known as a key regulator of stem cell migration to sites of tissue injury. A major enzyme mediating the degradation of SDF-1 is DPP4. Suppression of DPP4 enzymatic activities by pharmacological inhibitors preserves SDF-1, which results in enhanced homing of CXCR4⁺ progenitor cells from bone marrow to infarcted tissues. CNS central nervous system, ES embryonic stem