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Role of healing-specific-matricellular proteins and matrix metalloproteinases in age-related enhanced early remodeling after reperfused STEMI in dogs

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Abstract

We assessed whether aging augments left ventricular (LV) damage, remodeling, and dysfunction and alters expression of healing-specific-matricellular proteins (HSMPs), matrix metalloproteinases (MMPs) and other pertinent proteins after acute reperfused-ST-segment-elevation myocardial infarction (RSTEMI) in the dog model. The findings suggest a novel role for HSMPs, MMPs, and the other proteins in the age-related increase in LV damage, remodeling, and dysfunction. Potentially detrimental effects of the altered proteins appear to outweigh beneficial effects and contribute to adverse outcome. Deleterious changes include the increase in matrix-degrading MMPs, inducible nitric oxide synthase (iNOS) and pro-inflammatory cytokines interleukin (IL)-6 and tumor necrosis factor (TNF)-α, HSMPs such as secreted-protein-acidic-and-rich-in-cysteine (SPARC) and osteopontin (OPN), the blunted increase in endothelial-NOS (eNOS), and the decrease in IL-10 and neuronal NOS (nNOS). Potentially beneficial changes include increases in the HSMP secretory-leucocyte-protease-inhibitor (SLPI) and cytokine transforming growth factor (TGF)-β1. Targeting these proteins may mitigate enhanced LV remodeling and dysfunction with aging.

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Acknowledgements

This work was supported in part by grants from the Canadian Institutes of Health Research (CIHR) and Heart and Stroke Foundation of Canada (HSFC), Ottawa, Ontario. We thank C. Jugdutt for her assistance with manuscript preparation, and Mr. Vijayan Menon for his support with computer.

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Grants from CIHR and HSFC.

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Authors and Affiliations

  1. Division of Cardiology, Department of Medicine, 2C2 Walter MacKenzie Health Sciences Centre, University of Alberta, Edmonton, AB, Canada, T6G 2R7

    Bodh I. Jugdutt

  2. Cardiovascular Research Group, Faculty of Medicine, University of Alberta, Edmonton, Canada

    Bodh I. Jugdutt & Arivazhagan Palaniyappan

  3. Health Sciences Laboratory Animal Services, Faculty of Medicine, University of Alberta, Edmonton, Canada

    Richard R. E. Uwiera

  4. Department of Pathology and Laboratory Medicine, Faculty of Medicine, University of Alberta, Edmonton, Canada

    Halliday Idikio

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  1. Bodh I. Jugdutt
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  2. Arivazhagan Palaniyappan
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Correspondence to Bodh I. Jugdutt.

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Jugdutt, B.I., Palaniyappan, A., Uwiera, R.R.E. et al. Role of healing-specific-matricellular proteins and matrix metalloproteinases in age-related enhanced early remodeling after reperfused STEMI in dogs. Mol Cell Biochem 322, 25–36 (2009). https://doi.org/10.1007/s11010-008-9936-9

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