Effect of exercise training on cardiac function and glucose metabolism in the ischemic border zone: insights from multi-modal imaging techniques

Figure 1. Physiological effects of early exercise training in AMI rats. (A) Time course of body weight in the different groups of rats. (B–D) Body weight (BW), heart weight (HW), heart weight-to-body weight ratio (HW/BW) were recorded at the 8 weeks of exercise training. (E) Quantification of exercise exhaustion test (running distance) of Sham, MIC and MIE rats at the end point of experiment. **P < 0.01, ***P < 0.001. AMI, acute myocardial infarction.

Figure 2. Effects of exercise training on cardiac function measured by CMR. (A) Representative short-axis slices from cine CMR at end-diastole (top) and end-systole (bottom) of three groups after 8 weeks of exercise. (B) Time course of LV parameters in the three groups. Rats in the MIC and MIE groups underwent significant drops in LVEDV, SV, CO and LVEF compared to the sham group. LVEDV and LVEF increased obviously in the MIE group compared to the MIC group with the continued exercise training. (C) Representative 17-segment CMR data, arranged from left to right, show the Sham, MIC, and MIE groups at 8 weeks of exercise. Color and figure are representative the WT%. (D) WT% between end-diastole and end-systole demonstrated for each group. Blue lines represent the Sham group, yellow lines represent the MIE group and red lines represent the MIC group. Comparison between MIC and Sham: *P < 0.05. Comparison between MIE and MIC: †P < 0.05. LVEDV, left ventricular end-diastolic volume; SV, stroke volume; CO, cardiac output; LVEF, left ventricular eject fraction; WT%, wall thickening percentage.

Figure 3. Heart morphology and pathology of rats after 8 weeks of exercise. Representative images of hematoxylin-eosin (H&E) (A), Masson's trichrome (B) and WGA (C) in transversal sections of left ventricle of rats of the three groups. Scale bars, 5,000 μm (scale bar of the gross pathology slides of H&E, Masson's trichrome) and 50 μm (scale bar of the local pathology and WGA).

Figure 4. Changes of glucose uptake after AMI and effects of exercise. Myocardium glucose metabolism were assessed by 18F-FDG uptake using micro-PET at baseline (1 week after AMI), and 4, 8 weeks exercise training. Representative coronal, short axis, horizontal long-axis and vertical long-axis of 18F-FDG uptake in the three groups.

Figure 5. Quantitative analysis of 18F-FDG PET imaging. (A) Representative PET/CT images of the three groups of rats in the coronal and transverse planes after 8 weeks exercise training. (B,C) Quantitative analysis of SUV mean and SUV max achieved from 18F-FDG PET/CT scans in the three groups. *P < 0.05, **P < 0.01, *** P < 0.001.

Figure 6. Effects of exercise on the expressions of GLUT4 and PFKFB3 in myocardial tissues of rats after 8 weeks of exercise training. (A,C) Representative micrographs of heart sections from the ischemic border zones of the three groups. (B,D) Protein expressional levels of GLUT4 and PFKFB3 in the Sham, MIC and MIE groups. n = 4 rats per group. ***P < 0.001.

Figure 7. Results from RNA-Seq of myocardial tissue. (A,B) Volcano plots showing different expression genes (DEGs) between Sham and MIC, MIC and MIE respectively. (C) Twenty significantly enriched categories were identified through functional enrichment analysis of gene ontology (GO). Red line: Number of DEGs. Bars: Significance level. (D) The most highly significant pathways differentially regulated in metabolic pathways and cellular processes among the three groups. (E) KEGG enrichment analysis of metabolism pathways for genes showing upregulation (red) and downregulation (blue) in Sham, MIC and MIE rats. For volcano plots, grey represents nonsignificant, red indicates upregulated genes with P < 0.05, blue indicates downregulated genes with P < 0.05.

Figure 8. Effects of exercise training on metabolic pathways in myocardial tissue of rats after AMI. Protein expression levels of p-AMPK (A), GLUT4 (B), and PFKFB3 (C) in myocardial tissue of rats from three groups after 8 weeks of exercise training, as determined by Western blotting. Protein levels were normalized to glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Representative Western blot images for p-AMPK (D), GLUT4 (E), and PFKFB3 (F) are shown for each group. n = 4/group. **P < 0.01, **P < 0.001.