Expression and Role of Lubricin in the Human Pericardium: Implications as a Therapeutic to Prevent Post-Operative Adhesions
Abstract
Background Post-cardiac surgery retrosternal pericardial adhesions are associated with greater mortality risks with re-operations. Fibrous adhesion development is mediated by cardiac myofibroblasts. There is cause to... [ view full abstract ]
Background
Post-cardiac surgery retrosternal pericardial adhesions are associated with greater mortality risks with re-operations. Fibrous adhesion development is mediated by cardiac myofibroblasts. There is cause to suggest that lubricin (proteoglycan 4, PRG4), a mucin-like glycoprotein, may be expressed in human pericardial tissue.
Methods/Results:
Human pericardial tissue was obtained from cardiac surgery patients and tested by immunohistochemistry for expression of full-length PRG4. This is the first study to document expression of PRG4 in the human pericardial fluid and co-localization of expression by mesothelial cells lining the pericardial cavity. The role of full-length recombinant human lubricin (rhPRG4) in maintaining pericardial homeostasis was investigated in a cell adhesion assay. Human cardiac myofibroblasts were obtained from atrial appendage and seeded onto tissue culture plates coated with 100 µg/mL concentration of rhPRG4 and assessed for cell adhesion to the coated plates. rhPRG4 completely prevented myofibroblast adhesion (see Figure). The effects of rhPRG4 on myofibroblasts were tested in an in vitro model of wound contraction. Myofibroblasts were seeded in a 3D collagen matrix. Contraction percentage of the collagen matrix is proportional to myofibroblast activity. Myofibroblast activation was induced by pro-fibrotic cytokine, transforming growth factor – beta1 (TGF-β1). In the presence of TGF-β1, 250 µg/mL concentration rhPRG4 attenuated myofibroblast mediated matrix contraction (67.2% ± 1.9 vs 55.9% ± 2.2, p<0.05).
Conclusions:
For the first time, we document expression of full length PRG4 in human pericardial fluid and pericardial tissue. In vitro, rhPRG4 completely prevented adhesion of cardiac myofibroblasts and attenuated TGF-β1 mediated human cardiac myofibroblast activation.
Authors
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Daniel Park
(University of Calgary)
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Suresh Regmi
(University of Calgary)
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Daniyil Svystonyuk
(University of Calgary)
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Darrell Belke
(University of Calgary)
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Guoqi Teng
(University of Calgary)
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Holly Mewhort
(University of Calgary)
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David Guzzardi
(University of Calgary)
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Sean Kang
(University of Calgary)
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Tannin Schmidt
(University of Calgary)
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Paul Fedak
(University of Calgary)
Topic Area
Topics: Other
Session
Poster » Poster Presentations (18:30 - Thursday, 8th September, Max Bell 252)