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, Douglas McFadden, Alexandra Lucas

Research output: Contribution to journalArticle

76 Citations (Scopus)

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 - Jan 1 2000
Externally publishedYes

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Tunica Intima
Vascular System Injuries
Angioplasty
Chemokines
Hyperplasia
Carrier Proteins
Anti-Inflammatory Agents
Cytokines
Wounds and Injuries
Growth
Rabbits
CXC Chemokines
Myxoma
Atherosclerotic Plaques
Sprague Dawley Rats
Glycoproteins
Proteins
Therapeutics

ASJC Scopus subject areas

  • Medicine(all)

Cite this

The vital anti-inflammatory chemokine-binding protein M-T7 reduces intimal hyperplasia after vascular injury. / Liu, Liying; Lalani, Alshad; Dai, Erbin; Seet, Bruce; Macauley, Colin; Singh, Raj; Fan, Lilly; McFadden, Douglas; Lucas, Alexandra.

In: Journal of Clinical Investigation, Vol. 105, No. 11, 01.01.2000, p. 1613-1621.

Research output: Contribution to journalArticle

Liu, Liying ; Lalani, Alshad ; Dai, Erbin ; Seet, Bruce ; Macauley, Colin ; Singh, Raj ; Fan, Lilly ; McFadden, Douglas ; Lucas, Alexandra. / The vital anti-inflammatory chemokine-binding protein M-T7 reduces intimal hyperplasia after vascular injury. In: Journal of Clinical Investigation. 2000 ; Vol. 105, No. 11. pp. 1613-1621.
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