The viral anti-inflammatory chemokine-binding protein M-T7 reduces intimal hyperplasia after vascular injury.
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.
Liu
L
L
Vascular Biology Research Group, Robarts Research Institute, Department of Microbiology and Immunology, University of Western Ontario, London, Ontario, Canada.
Lalani
A
A
Dai
E
E
Seet
B
B
Macauley
C
C
Singh
R
R
Fan
L
L
McFadden
G
G
Lucas
A
A
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D018801:CD2 Antigens / Q000032:analysis; D018932:Chemokine CCL2 / Q000032:analysis; D054407:Chemokine CCL4; D018925:Chemokines / Q000037:antagonists & inhibitors*; D006493:Heparin / Q000494:pharmacology; D006965:Hyperplasia; D007150:Immunohistochemistry; D007371:Interferon-gamma / Q000032:analysis; D019402:Macrophage Inflammatory Proteins / Q000032:analysis; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000473:pathology; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D017471:Receptors, Interferon / Q000378:metabolism*; D014764:Viral Proteins / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D018801:CD2 Antigens; D018932:Chemokine CCL2; D054407:Chemokine CCL4; D018925:Chemokines; C091989:M-T7 protein, Myxoma virus; D019402:Macrophage Inflammatory Proteins; D017471:Receptors, Interferon; D014764:Viral Proteins; D007371:Interferon-gamma; D006493:Heparin