Project Details
Projekt
Heme oxygenase-1 as a therapeutic target in anti-HLA antibody-triggered transplant vasculopathy
Subject Area
Rheumatology
Term
from 2014 to 2021
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 265437184
Transplant vasculopathy (TV), a hallmark of chronic transplant rejection, is a major limiting factor for graft survival after heart and kidney transplantation, in which current therapeutic regimens are largely ineffective. TV is characterized by rapid narrowing of allograft vessels with progressive ischemia and graft failure. Ligation of de novo anti-HLA antibodies with the vascular endothelium plays a key role in the pathogenesis of this disorder. Similar to atherosclerosis, TV is characterized by increased cell proliferation and chronic inflammation of arteries. As inflammation is closely associated with oxidative stress, regulation of the vascular redox homeostasis appears to be critical in the pathogenesis of TV. The antioxidant inducible enzyme heme oxygenase (HO)-1 has major anti-inflammatory effects mediated by metabolic degradation of proinflammatory free heme as well as production of carbon monoxide (CO) and biliverdin. In addition, overexpression of HO-1 has been shown to be beneficial in various experimental models of inflammation and transplantation. The goal of this proposal is to gain a comprehensive understanding on the role of HO-1 in vascular cells for the pathogenesis and therapy of anti-HLA antibody-triggered TV. In particular, the therapeutic potential of pre-emptive pharmacological targeting to HO-1 in this disorder will be investigated.
DFG Programme
Research Grants
