Basic Research in Cardiology

, 112:57 | Cite as

Methylglyoxal-derived advanced glycation end products contribute to negative cardiac remodeling and dysfunction post-myocardial infarction

  • Nick J. R. Blackburn
  • Branka Vulesevic
  • Brian McNeill
  • Cagla Eren Cimenci
  • Ali Ahmadi
  • Mayte Gonzalez-Gomez
  • Aleksandra Ostojic
  • Zhiyuan Zhong
  • Michael Brownlee
  • Paul J. Beisswenger
  • Ross W. Milne
  • Erik J. SuuronenEmail author
Original Contribution


Advanced glycation end-products (AGEs) have been associated with poorer outcomes after myocardial infarction (MI), and linked with heart failure. Methylglyoxal (MG) is considered the most important AGE precursor, but its role in MI is unknown. In this study, we investigated the involvement of MG-derived AGEs (MG-AGEs) in MI using transgenic mice that over-express the MG-metabolizing enzyme glyoxalase-1 (GLO1). MI was induced in GLO1 mice and wild-type (WT) littermates. At 6 h post-MI, mass spectrometry revealed that MG-H1 (a principal MG-AGE) was increased in the hearts of WT mice, and immunohistochemistry demonstrated that this persisted for 4 weeks. GLO1 over-expression reduced MG-AGE levels at 6 h and 4 weeks, and GLO1 mice exhibited superior cardiac function at 4 weeks post-MI compared to WT mice. Immunohistochemistry revealed greater vascular density and reduced cardiomyocyte apoptosis in GLO1 vs. WT mice. The recruitment of c-kit+ cells and their incorporation into the vasculature (c-kit+CD31+ cells) was higher in the infarcted myocardium of GLO1 mice. MG-AGEs appeared to accumulate in type I collagen surrounding arterioles, prompting investigation in vitro. In culture, the interaction of angiogenic bone marrow cells with MG-modified collagen resulted in reduced cell adhesion, increased susceptibility to apoptosis, fewer progenitor cells, and reduced angiogenic potential. This study reveals that MG-AGEs are produced post-MI and identifies a causative role for their accumulation in the cellular changes, adverse remodeling and functional loss of the heart after MI. MG may represent a novel target for preventing damage and improving function of the infarcted heart.


Advanced glycation end-products Bone marrow cells Extracellular matrix Glyoxalase-1 Methylglyoxal Myocardial infarction 



The authors would like to thank Rick Seymour and Suzanne Crowe (University of Ottawa Heart Institute) for technical support. This work was supported by operating Grants from the Heart and Stroke Foundation of Canada (HSFC; GIA-000225), and the Canadian Institutes of Health Research (CIHR; FRN 125678). Nick Blackburn was supported by a University of Ottawa Faculty of Medicine Endowed Fund for Cardiac Research and the UOHI Foundation; Branka Vulesevic by a Canadian Graduate Scholarship from the CIHR; and Brian McNeill by a Research Fellowship Award from the HSFC.

Compliance with ethical standards

Conflict of interest

PJB has a financial interest in PreventAGE Healthcare, where the mass spectrometry of MG-AGEs was performed. The authors declare no other potential conflicts of interest.


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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Nick J. R. Blackburn
    • 1
    • 2
  • Branka Vulesevic
    • 1
    • 2
  • Brian McNeill
    • 1
  • Cagla Eren Cimenci
    • 1
    • 2
  • Ali Ahmadi
    • 1
    • 2
  • Mayte Gonzalez-Gomez
    • 1
    • 2
  • Aleksandra Ostojic
    • 1
    • 2
  • Zhiyuan Zhong
    • 3
  • Michael Brownlee
    • 4
  • Paul J. Beisswenger
    • 5
  • Ross W. Milne
    • 6
  • Erik J. Suuronen
    • 1
    • 2
    Email author
  1. 1.Division of Cardiac SurgeryUniversity of Ottawa Heart InstituteOttawaCanada
  2. 2.Department of Cellular and Molecular MedicineUniversity of OttawaOttawaCanada
  3. 3.Biomedical Polymers Laboratory, and Jiangsu Key Laboratory of Advanced Functional Polymer Design and Application, College of Chemistry, Chemical Engineering and Materials ScienceSoochow UniversitySuzhouChina
  4. 4.Diabetes Research Center and Departments of Internal Medicine and PathologyAlbert Einstein College of MedicineBronxUSA
  5. 5.Geisel School of Medicine at DartmouthPreventAGE HealthcareLebanonUSA
  6. 6.Diabetes and Atherosclerosis LaboratoryUniversity of Ottawa Heart InstituteOttawaCanada

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