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Molecular and Cellular Biochemistry

, Volume 321, Issue 1–2, pp 9–22 | Cite as

Comparison of vasopeptidase inhibitor omapatrilat and angiotensin receptor blocker candesartan on extracellular matrix, myeloperoxidase, cytokines, and ventricular remodeling during healing after reperfused myocardial infarction

  • Arivazhagan Palaniyappan
  • Richard R. E. Uwiera
  • Halliday Idikio
  • Bodh I. Jugdutt
Article

Abstract

We determined effects of the vasopeptidase inhibitor (VPI) omapatrilat and angiotensin II type 1 receptor (AT1R) blocker (ARB) candesartan in rats during healing between day-2 and day-21 after reperfused myocardial infarction (RMI) on left ventricular (LV) remodeling and function, and regional matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP (TIMP)-3, inducible-nitric-oxide-synthase (iNOS), oxidant-generating myeloperoxidase (MPO), and cytokines tumor-necrosis-factor (TNF)-α, interleukin (IL)-6 and IL-10, and transforming-growth-factor (TGF)-β1, and collagens. Compared to RMI-placebo, both agents reversed adverse LV remodeling and systolic and diastolic dysfunction, improved collagen remodeling, and normalized MMP-9 (activity, protein, and mRNA), TIMP-3 (protein and mRNA), and iNOS, MPO, TNF-α, IL-6, and TGF-β1 proteins, and improved MMP-9/TIMP-3 balance and IL-10 levels in previously ischemic zones. The results suggest that modulation of matrix proteases, oxidants, cytokines, and NOSs with omapatrilat and candesartan contribute to reversal of adverse collagen and LV remodeling and attenuation of LV dysfunction during healing after RMI.

Keywords

Vasopeptidase inhibitor Angiotensin II type 1 receptor blocker Extracellular matrix Myeloperoxidase Cytokines Ventricular remodeling Reperfused myocardial infarction 

Notes

Acknowledgements

This work was supported in part by a grant from the Heart and Stroke Foundation of Canada. We thank Astra Pharma Inc. (Mississauga, Ontario, Canada) and Bristol-Myers Squibb Co. (Saint-Laurent, Quebec, Canada) for supplying candesartan and omapatrilat, respectively. We are indebted to C. Jugdutt for manuscript preparation and Mr. Vijayan Menon for computer support.

Disclosure: Gift of drugs from Industry and small operating grant from HSFC.

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Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Arivazhagan Palaniyappan
    • 1
  • Richard R. E. Uwiera
    • 2
  • Halliday Idikio
    • 3
  • Bodh I. Jugdutt
    • 1
    • 4
  1. 1.Cardiovascular Research Group, Faculty of MedicineUniversity of AlbertaEdmontonCanada
  2. 2.Health Sciences Laboratory Animal Services, Faculty of MedicineUniversity of AlbertaEdmontonCanada
  3. 3.Department of Pathology and Laboratory Medicine, Faculty of MedicineUniversity of AlbertaEdmontonCanada
  4. 4.2C2 Walter C. Mackenzie, Cardiology Division of the Department of Medicine, Faculty of MedicineUniversity of AlbertaEdmontonCanada

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