Abstract
Chronic rejection remains a major obstacle in transplant medicine. Recent studies suggest a crucial role of the chemokine SDF-1 on neointima formation after injury. Here, we investigate the potential therapeutic effect of inhibiting the SDF-1/CXCR4/CXCR7 axis with an anti-SDF-1 Spiegelmer (NOX-A12) on the development of chronic allograft vasculopathy. Heterotopic heart transplants from H-2bm12 to B6 mice and aortic transplants from Balb/c to B6 were performed. Mice were treated with NOX-A12. Control animals received a nonfunctional Spiegelmer (revNOX-A12). Samples were retrieved at different time points and analysed by histology, RT-PCR and proliferation assay. Blockade of SDF-1 caused a significant decrease in neointima formation as measured by intima/media ratio (1.0±0.1 vs. 1.8±0.1, P<0.001 AoTx; 0.35±0.05 vs. 1.13±0.27, P<0.05 HTx). In vitro treatment of primary vascular smooth muscle cells with NOX-A12 showed a significant reduction in proliferation (0.42±0.04 vs. 0.24±0.03, P<0.05). TGF-β, TNF-α and IL-6 levels were significantly reduced under SDF-1 inhibition (3.42±0.37 vs. 1.67±0.33, P<0.05; 2.18±0.37 vs. 1.0±0.39, P<0.05; 2.18±0.26 vs. 1.6±0.1, P<0.05). SDF-1/CXCR4/CXCR7 plays a critical role in the development of chronic allograft vasculopathy (CAV). Therefore, pharmacological inhibition of SDF-1 with NOX-A12 may represent a therapeutic option to ameliorate chronic rejection changes.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
