Abstract |
Chemokines and IFN-gamma 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-gamma 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.
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Authors | L Liu, A Lalani, E Dai, B Seet, C Macauley, R Singh, L Fan, G McFadden, A Lucas |
Journal | The Journal of clinical investigation
(J Clin Invest)
Vol. 105
Issue 11
Pg. 1613-21
(Jun 2000)
ISSN: 0021-9738 [Print] United States |
PMID | 10841520
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Anti-Inflammatory Agents
- CD2 Antigens
- Chemokine CCL2
- Chemokine CCL4
- Chemokines
- M-T7 protein, Myxoma virus
- Macrophage Inflammatory Proteins
- Receptors, Interferon
- Viral Proteins
- Interferon-gamma
- Heparin
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Topics |
- Animals
- Anti-Inflammatory Agents
(pharmacology)
- CD2 Antigens
(analysis)
- Chemokine CCL2
(analysis)
- Chemokine CCL4
- Chemokines
(antagonists & inhibitors)
- Heparin
(pharmacology)
- Hyperplasia
- Immunohistochemistry
- Interferon-gamma
(analysis)
- Macrophage Inflammatory Proteins
(analysis)
- Muscle, Smooth, Vascular
(drug effects, pathology)
- Rabbits
- Rats
- Rats, Sprague-Dawley
- Receptors, Interferon
(metabolism)
- Viral Proteins
(metabolism)
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