Supplementary Materials

Supplementary Material for:

Accumulation of 5-oxoproline in myocardial dysfunction and the protective effects of OPLAH

Atze van der Pol, Andres Gil, Herman H. W. Silljé, Jasper Tromp, Ekaterina S. Ovchinnikova, Inge Vreeswijk-Baudoin, Martijn Hoes, Ibrahim J. Domian, Bart van de Sluis, Jan M. van Deursen, Adriaan A. Voors, Dirk J. van Veldhuisen, Wiek H. van Gilst, Eugene Berezikov, Pim van der Harst, Rudolf A. de Boer, Rainer Bischoff, Peter van der Meer*

*Corresponding author. Email: p.van.der.meer{at}umcg.nl

Published 8 November 2017, Sci. Transl. Med. 9, eaam8574 (2017)
DOI: 10.1126/scitranslmed.aam8574

This PDF file includes:

  • Materials and Methods
  • Fig. S1. Top 29 novel cardiac fetal genes mRNA expression profiles across a human organ panel.
  • Fig. S2. OPLAH is localized in the cytosol of cardiomyocytes.
  • Fig. S3. OPLAH protein expression in HF animal models.
  • Fig. S4. Mechanical stretch results in oxidative stress and OPLAH depletion in NRVCs.
  • Fig. S5. Hypoxia induces oxidative stress and OPLAH depletion in NRVCs.
  • Fig. S6. H2O2 induces oxidative stress and OPLAH depletion in NRVCs.
  • Fig. S7. OPLAH short hairpin and overexpression constructs in NRVCs.
  • Fig. S8. ERRα is involved in the regulation of OPLAH in NRVCs.
  • Fig. S9. ERRα expression in NRVCs exposed to stretch, hypoxia, or H2O2.
  • Fig. S10. OPLAH-TG mice have reduced fibrosis compared to WT mice after IR injury.
  • Fig. S11. OPLAH-TG mice show no difference in LV hypertrophy compared to WT mice after IR injury or after MI.
  • Fig. S12. OPLAH-TG mice have reduced cleaved Caspase-3–positive cells in the left ventricle after MI.
  • Fig. S13. Schematic of OPLAH regulation in the cardiomyocyte.
  • Fig. S14. Calibration curves for LC-MS ISs 13C-5-oxoproline and L-glutamic acid.
  • Table S4. Characteristics of renin overexpression rats (REN2) and Sprague Dawley rats.
  • Table S5. Characteristics of WT mice after IR injury.
  • Table S6. Characteristics of Sprague Dawley rats after MI.
  • Table S7. Characteristics of OPLAH overexpression (TG) and WT mice at baseline (sham) and after IR injury.
  • Table S8. Characteristics of OPLAH overexpression (TG) and WT mice at baseline (sham) and after MI.
  • Table S9. Baseline characteristics of all 535 patients compared to total COACH cohort (n = 1023).
  • Table S10. Baseline characteristics of all 535 patients at discharge, divided into tertiles of 5-oxoproline (in micromolars).
  • Table S11. Regression analyses of 5-oxoproline association with HF biomarkers.
  • Table S12. Regression analyses of multivariable model corrected for univariable associations.
  • Table S13. Survival analyses.
  • Table S14. OPLAH-specific shRNA–targeting oligonucleotides and cloning primers for human OPLAH overexpression.
  • Table S15. List of primers used in this study.
  • Table S16. List of antibodies used in this study.
  • Table S17. Accuracy and precision results for 5-oxoproline.
  • Table S18. Accuracy and precision results for L-glutamic acid.

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Other Supplementary Material for this manuscript includes the following:

  • Table S1. Significantly up-regulated genes during murine cardiac development (provided as an Excel file).
  • Table S2. Significantly down-regulated genes during murine cardiac development (provided as an Excel file).
  • Table S3. Top cardiac fetal reprogramming genes (provided as an Excel file).
  • Table S19. Individual subject level data for experiments with n < 20 (provided as an Excel file).

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