Fig 1.
Heat map of myocardial metabolome.
The data obtained by multi-platform metabolomics (GC/MS, MS/MS, HPLC) and presented as fold change in SHF and DHF as compared to Control. Green indicates a significant decrease, and read indicates a significant increase in the level of metabolite as compared to Control. BCAA: branched-chain amino acid, PPP: pentose phosphate pathway, GSH: glutathione, GC/MS: gas-chromatography/mass-spectrometry, MS/MS: tandem mass-spectrometry, HPLC: high performance liquid chromatography.
Table 1.
Hemodynamics of SHF and DHF in pre- and post-tachypacing.
Fig 2.
Heat map of selected metabolic proteome.
Metabolism-related proteins detected by LC-MS/MS, and presented as fold change in SHF and DHF compared with those from Control. Green indicates a significant decrease, and read indicates a significant increase in the level of protein expression as compared to Control.
Fig 3.
High-energy phosphates and related adenine nucleotides.
Metabolites were measured by HPLC in Control, SHF and DHF hearts. A-C. Chromatograms of extracts from ventricular tissue in Control (A), SHF (B), and DHF (C). D-I. Quantitative analysis of the levels of creatine (Cr), phosphocreatine (PCr), ATP, ADP, AMP, and NAD+, respectively, normalized by wet tissue weight. J. PCr/ATP ratio. K. Total pool of myocardial creatine (creatine + PCr). L. Total pool of adenine nucleotides (ATP+ADP+AMP). *p<0.05.
Fig 4.
Protein expression of creatine kinase (CK) isoforms.
Both cytosolic CK-B type (A) and mitochondrial CK (B) are upregulated in SHF and DHF as compared to Control. *p<0.05.
Fig 5.
Metabolomic and proteomic profile of the TCA cycle.
Data from Control, SHF, and DHF hearts. Filled bars: the TCA cycle intermediates. Open bars: the TCA cycle enzymes. Metabolome is presented in arbitrary units while proteome is presented as fold change compared to Control. BCAA: branched-chain amino acids. *P<0.05.
Fig 6.
A schematic overview of fatty acid catabolism is presented with the levels of detected metabolites and relevant proteins in Control, SHF, and DHF. Detected metabolites and proteins are indicated with bold font. Blue color indicates enzymes involved in fatty acid oxidation. Metabolome is presented in arbitrary units while proteome is presented as fold change compared to Control. Filled bars: metabolites, Open bars: proteins. OCTN2: organic cation transporter novel type 2, FATP: fatty acid transport protein, FABP: fatty acid binding protein, CPT1: carnitine palmitoyltransferase I, CPT2: carnitine palmitoyltransferase II, CACT: carnitine O-acetyltransferase; DH: dehydrogenase; ETF: electron-transferring flavoprotein; ETFDH: electron transfer flavoprotein-ubiquinone oxidoreductase; CRAT: carnitine O-acetyltransferase. *P<0.05.
Fig 7.
Quantitative analysis of myocardial carnitine and acylcarnitines.
Majority of acylcarnitines were significantly reduced in both SHF and DHF as compared to Control (see also S3 Fig. for the levels of plasma acylcarnitines). P*<0.05
Fig 8.
Metabolomic and proteomic profile of glucose metabolism.
Data from Control, SHF, and DHF hearts. Detected metabolites and enzymes are indicated with bold font. Metabolome is presented in arbitrary units while proteome is presented as fold change compared to Control. Filled bars: metabolites. Open bars: proteins. G1-P: glucose 1-phosphate, G6-P: glucose 6-phosphate, F6-P: fructose 6-phosphate, F1,6-P: fructose 1,6-bisphosphate, GAP: glycealdehydo 3-phosphate, DHAP: dihydroxyacetone phosphate, 1,3-PG: 1,3-bisphosphoglycerate, 3-PG: 3-phosphoglycerate, 2-PG: 2-phosphoglycerate, PEP: phosphoenolpyruvate. P*<0.05.