Inhibition of MCP-1/CCR2 signaling does not inhibit intimal proliferation in a mouse aortic transplant model.
BACKGROUND
Transplant arteriopathy is the leading cause of long term morbidity and mortality following heart transplantation. Animal models have demonstrated that monocyte chemoattractant protein (MCP)-1 is induced early after transplant in cardiac and aortic allografts. We have previously reported that deficiency of MCP-1 or its receptor, CC chemokine receptor 2 (CCR2), is associated with a reduction in intimal proliferation in a mouse femoral artery injury model. Using knockout mice, we have now examined the role of MCP-1 and CCR2 in the development of the intimal proliferation of transplant arteriopathy.


METHODS
C57Bl/6 CCR2 and MCP-1 wild-type and knockout mice were used in the studies and aortic transplants were performed between Balb/c mice and C57Bl/6 mice. Aortas from recipient animals were harvested 8 weeks after transplant.


RESULTS
Unlike arterial injury, in an aortic transplant model inhibition of MCP-1/CCR2 signaling did not result in reduced intimal proliferation.


CONCLUSIONS
Despite a pathology that appears similar, the inflammatory mediators that regulate transplant arteriopathy differ from those regulating intimal proliferation secondary to wire injury. Our results suggest that targeting MCP-1/CCR2 signaling is not sufficient to block transplant arteriopathy across a complete MHC-mismatch barrier.
Alexis
Jeffrey D
JD
Aab Cardiovascular Research Institute, University of Rochester School of Medicine and Dentistry, Rochester, NY 14586, USA. jeffrey_alexis@urmc.rochester.edu
Pyo
Robert T
RT
Chereshnev
Igor
I
Katz
Jonathan
J
Rollins
Barrett J
BJ
Charo
Israel F
IF
Taubman
Mark B
MB
D000818:Animals; D001011:Aorta / Q000276:immunology / Q000473:pathology* / Q000637:transplantation*; D001018:Aortic Diseases / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D049109:Cell Proliferation; D018932:Chemokine CCL2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D006965:Hyperplasia; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016377:Organ Transplantation / Q000009:adverse effects; D054390:Receptors, CCR2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000276:immunology; D017539:Tunica Intima / Q000276:immunology / Q000473:pathology*
C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; D018932:Chemokine CCL2; D054390:Receptors, CCR2