The vital anti-inflammatory chemokine-binding protein M-T7 reduces intimal hyperplasia after vascular injury

Liying Liu, Alshad Lalani, Erbin Dai, Bruce Seet, Colin Macauley, Raj Singh, Lilly Fan, Grant McFadden, Alexandra Lucas

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Abstract

Chemokines and IFN-γ function as central regulators of inflammatory responses to vascular injury. Both classes of cytokines are upregulated during restenosis, a response to vascular injury that leads to recurrent atherosclerotic plaque growth, but the relative impact of each class of cytokines remains undetermined. M-T7 is a secreted myxoma viral immunomodulatory glycoprotein that functions both as a species-specific inhibitor of rabbit IFN-γ and as a chemokine-binding protein, interacting with a wide range of C, C-C, and C-X-C chemokines in a species-nonspecific fashion. We wished to (a) assess the efficacy of purified M-T7 protein in inhibiting intimal hyperplasia after angioplasty injury and (b) exploit unique species-specific functions of M-T7 in order to judge the relative importance of each cytokine class on plaque growth. Anesthetized New Zealand white rabbits and Sprague-Dawley rats received either M-T7 or control at the time of arterial angioplasty injury. Histological analysis at 28 days demonstrated significant reductions in intimal hyperplasia with M-T7 treatment in both models, with an associated early inhibition of inflammatory cell invasion. Purified M-T7 protein inhibits intimal hyperplasia after angioplasty injury in a species-nonspecific fashion, thus implicating the chemokine-binding activity as more critical for prevention of plaque growth after vascular injury.

Original languageEnglish (US)
Pages (from-to)1613-1621
Number of pages9
JournalJournal of Clinical Investigation
Volume105
Issue number11
DOIs
StatePublished - Jun 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Medicine(all)

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