Myxomavirus anti-inflammatory chemokine binding protein reduces the increased plaque growth induced by chronic Porphyromonas gingivalis oral infection after balloon angioplasty aortic injury in mice.

Abstract

Thrombotic occlusion of inflammatory plaque in coronary arteries causes myocardial infarction. Treatment with emergent balloon angioplasty (BA) and stent implant improves survival, but restenosis (regrowth) can occur. Periodontal bacteremia is closely associated with inflammation and native arterial atherosclerosis, with potential to increase restenosis. Two virus-derived anti-inflammatory proteins, M-T7 and Serp-1, reduce inflammation and plaque growth after BA and transplant in animal models through separate pathways. M-T7 is a broad spectrum C, CC and CXC chemokine-binding protein. Serp-1 is a serine protease inhibitor (serpin) inhibiting thrombotic and thrombolytic pathways. Serp-1 also reduces arterial inflammation and improves survival in a mouse herpes virus (MHV68) model of lethal vasculitis. In addition, Serp-1 demonstrated safety and efficacy in patients with unstable coronary disease and stent implant, reducing markers of myocardial damage. We investigate here the effects of Porphyromonas gingivalis, a periodontal pathogen, on restenosis after BA and the effects of blocking chemokine and protease pathways with M-T7 and Serp-1. ApoE-/- mice had aortic BA and oral P. gingivalis infection. Arterial plaque growth was examined at 24 weeks with and without anti-inflammatory protein treatment. Dental plaques from mice infected with P. gingivalis tested positive for infection. Neither Serp-1 nor M-T7 treatment reduced infection, but IgG antibody levels in mice treated with Serp-1 and M-T7 were reduced. P. gingivalis significantly increased monocyte invasion and arterial plaque growth after BA (P<0.025). Monocyte invasion and plaque growth were blocked by M-T7 treatment (P<0.023), whereas Serp-1 produced only a trend toward reductions. Both proteins modified expression of TLR4 and MyD88. In conclusion, aortic plaque growth in ApoE-/- mice increased after angioplasty in mice with chronic oral P. gingivalis infection. Blockade of chemokines, but not serine proteases significantly reduced arterial plaque growth, suggesting a central role for chemokine-mediated inflammation after BA in P. gingivalis infected mice.

• Authors: Alexandra R Lucas, Raj K Verma, Erbin Dai, Liying Liu, Hao Chen, Sheela Kesavalu, Mercedes Rivera, Irina Velsko, Sriram Ambadapadi, Sasanka Chukkapalli, Lakshmyya Kesavalu
• Journal: PloS one (PLoS One) Vol. 9 Issue 10 Pg. e111353 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25354050 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• M-T7 protein, Myxoma virus
• Receptors, Interferon
• Viral Proteins
• alpha 1-Antitrypsin

Topics

• Angioplasty, Balloon (adverse effects)
• Animals
• Aorta (drug effects, surgery)
• Bacteroidaceae Infections (complications, drug therapy)
• Dental Plaque (drug therapy, microbiology)
• Mice
• Plaque, Atherosclerotic (drug therapy, microbiology)
• Porphyromonas gingivalis (pathogenicity)
• Receptors, Interferon (therapeutic use)
• Viral Proteins (pharmacology, therapeutic use)
• alpha 1-Antitrypsin (pharmacology, therapeutic use)