Integrated metabolomic profiling reveals metabolomic responses by epicardial and myocardial stromal cells to ischemia.

Figures

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  Fig. 1. Schematic representation of the overall approach and workflow of the study. Briefly, the EATDS and VSCs were harvested from the EAT (epicardial adipose tissue) and LV (left ventricle) respectively, challenged under ischemia, performed metabolite screening using LC-MS and the interconnecting mediators and pathways were determined using MSEA and network analysis. The EATDS and VSCs were treated with highly regulated mediators to assess the cardiac regenerative genes

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  Fig. 2. A Bar diagram showing 65 metabolites detected in the ischemic EATDS based on the Log2 FC. B MetaboAnalyst 6.0 pathway enrichment analysis of metabolites significantly downregulated (FC − 2 to − 4) in ischemia challenged EATDS (p < 0.05). C MSEA using MetaboAnalyst 6.0 showing significantly impacted pathways on -log10(p) associated with the metabolites (FC − 2 to − 4) (data in Table S3a). D MetaboAnalyst 6.0 pathway enrichment analysis of metabolites significantly downregulated (FC<−4) in ischemia challenged EATDS (p < 0.05). E MSEA using MetaboAnalyst 6.0 showing significantly impacted pathways on -log10(p) associated with the metabolites (FC < 4) (data in Table S3b). Metabolite-gene-disease interaction network associated with F moderately downregulated and G highly downregulated metabolites in EATDS. Metabolite-metabolite interaction network associated with H moderately downregulated and I highly downregulated metabolites in EATDS

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  Fig. 3. A MetaboAnalyst 6.0 pathway enrichment analysis of metabolites significantly upregulated in ischemia challenged EATDS (p < 0.05). B MSEA using MetaboAnalyst 6.0 showing significantly impacted pathways on -log10(p) associated with the upregulated metabolites in EATDS (data in Table S3c). C Metabolite-gene-disease interaction network and D metabolite-metabolite interaction network associated with upregulated metabolites in EATDS. The pathways enriched based on E metabolite-gene-disease interaction network and F metabolite-metabolite interaction network

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  Fig. 4. A Bar diagram showing 68 metabolites detected in the ischemic VSCs based on the Log2 FC. B MetaboAnalyst 6.0 pathway enrichment analysis of metabolites significantly downregulated (FC < 2) in ischemia challenged VSCs (p < 0.05). C MSEA using MetaboAnalyst 6.0 showing significantly impacted pathways on -log10(p) associated with the metabolites in VSCs (FC < 2) (data in Table S5a). D Metabolite-gene-disease interaction network and F metabolite-metabolite interaction network associated with downregulated metabolites in VSCs. The pathways enriched based on E metabolite-gene-disease interaction network and G metabolite-metabolite interaction network

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  Fig. 5. A MetaboAnalyst 6.0 pathway enrichment analysis of metabolites significantly upregulated in ischemia challenged VSCs (p < 0.05). B MSEA using MetaboAnalyst 6.0 showing significantly impacted pathways on -log10(p) associated with the upregulated metabolites in VSCs (data in Table S5b). C Metabolite-gene-disease interaction network and D metabolite-metabolite interaction network associated with upregulated metabolites in VSCs. The pathways enriched based on E metabolite-gene-disease interaction network and F metabolite-metabolite interaction network

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  Fig. 6. Gene expression analysis of VSCs and EATDS treated with A sarcosine, B (R)-(+)−2-Pyrrolidone-5-carboxylic acid and C hydroxypropionic acid showing the altered expression of the cardiac regenerative genes GATA4, NKX2.5, TROP-I, LGALS1, TBX5, and IRX4