Evidence of an interaction between TGF-β1 and the SDF-1/CXCR4/CXCR7 axis in human platelets. Issue 144 (August 2016)

• Record Type: Journal Article
• Authors: Rath, Dominik; Chatterjee, Madhumita; Holtkamp, Annabell; Tekath, Nina; Borst, Oliver; Vogel, Sebastian; Müller, Karin; Gawaz, Meinrad; Geisler, Tobias
• Is Part Of: Thrombosis research. Issue 144(2016)
• Page Start: 79
• Page End: 84
• Publication Date: 2016-08
• Subjects: CXCL12 -- CXCR4 -- CXCR7 protein, human -- TGFbeta1 -- Platelets; Thrombosis -- Periodicals; 616.135
• DOI: 10.1016/j.thromres.2016.06.006
• Languages: English
• ISSNs: 0049-3848

Abstract

Abstract: Background: TGF-β1, SDF-1 and its cognate receptors CXCR4 and CXCR7 are expressed on the surface of human platelets and their expression levels are differently regulated in symptomatic coronary artery disease (CAD). All these proteins and receptors influence outcome in patients with symptomatic CAD. There might be a crosstalk between TGF-β1 and the SDF-1/CXCR4/CXCR7 axis. Interrelations in CAD, especially in the context of platelets, are poorly understood. Therefore, we aimed to provide clinical and experimental evidence of interactions between TGF-β1 and the SDF-1/CXCR4/CXCR7 axis in human platelets. Methods and results: Blood samples of the complete cohort (n = 284) were analysed for platelet surface expression levels of TGF-β1, SDF-1, CXCR4 and CXCR7 by flow cytometry. For stimulation assays platelet rich plasma was treated with TGF-β1 or SDF-1 and then analysed by flow cytometry. Multiple regression analyses were run to show independent associations of TGF-β1 with SDF-1, CXCR4, CXCR7 and clinical cofactors. Both, CXCR4 and CXCR7 significantly predicted TGF-β1 (p < 0.001 and p < 0.001, respectively). After stimulation with SDF-1, surface expression of TGF-β1 increased significantly when compared to resting platelets [mean TGF-β1 MFI 19.01 vs. mean TGF-β1 MFI 14.01, p < 0.001]. Upon receptor blocking with either anti-CXCR4 or anti-CXCR7 monoclonal antibodies the enhancing effect of SDF-1 on TGF-β1 surface expression was significantly blunted. Stimulation with TGF-β1 did not alter SDF-1, CXCR4 or CXCR7 expression significantly. Conclusions: We provide first clinical and experimental data suggesting a cross-talk between TGF-β and the SDF-1/CXCR4/CXCR7 axis in platelets which does not involve transcriptional modulation as shown previously for other cellular systems. Highlights: Platelet surface expression of TGF-β1 correlates with platelet surface expression of SDF-1 and its receptors CXCR4 and CXCR7 in patients with symptomatic coronary artery disease Both, CXCR4 and CXCR7 are independently associated with TGF-β1 levelsPlatelet surface expression of TGF-β1 increases significantly after stimulation of platelets with recombinant SDF-1 in vitro SDF-1 induced TGF-β1 degranulation is diminished by blocking of either CXCR4 or CXCR7