Blockade of p38 MAPK inhibits chronic allograft vasculopathy.
Long-term survival after solid-organ transplantation is hampered by chronic changes in the arteries of the grafts, called chronic allograft vasculopathy (CAV). The lesions consist mainly of proliferating vascular smooth muscle cells that cause narrowing of the vessels; these lesions can develop within a few months. There is no effective treatment to prevent CAV. We previously noted that the pharmacological inhibition of p38 mitogen-activated protein kinase (MAPK) suppresses the proliferation of vascular smooth muscle cells. We hypothesized that in vivo inhibition of p38 MAPK in mice bearing allogeneic aortic allografts would prevent CAV. We here report that blockade of p38 MAPK, a signaling molecule involved in cell division, apoptosis, and cell death, markedly suppresses CAV. Given recent data indicating that inhibition of p38 MAPK is a promising approach for the treatment of autoimmune diseases plus our present findings, p38 MAPK blockade for CAV seems a reasonable approach to consider for clinical application.
Ollinger
Robert
R
Department of General and Transplant Surgery, D. Swarovski Research Lab, Medical University Innsbruck, Innsbruck, Austria. robert.oellinger@i-med.ac.at
Thomas
Michael
M
Kogler
Pamela
P
Hermann
Martin
M
Weiss
Helmut
H
Mark
Walter
W
Bilban
Martin
M
Troppmair
Jakob
J
Bach
Fritz H
FH
Margreiter
Raimund
R
D000818:Animals; D001011:Aorta / Q000637:transplantation*; D015704:CD4 Antigens / Q000032:analysis; D016827:CD8 Antigens / Q000032:analysis; D006085:Graft Survival; D007093:Imidazoles / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D010766:Phosphorylation; D011743:Pyrimidines / Q000627:therapeutic use*; D051381:Rats; D014184:Transplantation, Homologous / Q000276:immunology / Q000473:pathology*; D014652:Vascular Diseases / Q000517:prevention & control*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors*
D015704:CD4 Antigens; D016827:CD8 Antigens; D007093:Imidazoles; D011743:Pyrimidines; D048051:p38 Mitogen-Activated Protein Kinases; C406525:SB 239063