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28 Remote ischaemic conditioning involves signalling via CXCR4 but does not increase circulating levels of its known ligands
  1. DI Bromage,
  2. M Pillai,
  3. SM Davidson,
  4. DM Yellon
  1. The Hatter Cardiovascular Institute, University College London, 67 Chenies Mews, London, WC1E 6HX, UK

Abstract

Rationale for the study The CXC chemokine receptor 4 (CXCR4) has been implicated in acute cardioprotection from ischaemia-reperfusion injury conferred by remote ischaemic conditioning (RIC). CXCR4 has two known ligands, namely Stromal Derived Factor-1α (SDF1α) and Macrophage Migration Inhibitory Factor (MIF). We have previously demonstrated that total SDF-1α increases significantly after RIC in a murine model.1 Using a novel antibody specific to the active form of SDF-1α, we measured circulating SDF-1α and MIF after RIC to ascertain their involvement in RIC.

Methodology In contrast to our previous study, rats were ventilated with supplementary oxygen. Animals were randomly allocated to receive either RIC (3 × 5 min hind limb ischaemia) or sham. Total and active SDF-1α together with MIF were measured in plasma by ELISA. In a separate experiment, healthy, normoxic human volunteers were subjected to RIC (3 × 5 min arm ischaemia), and samples taken for ELISA and FACS analysis of platelet SDF-1α expression.

Results RIC did not significantly affect total SDF-1α in either rats or humans, while active SDF-1α was significantly reduced in human volunteers. MIF was unchanged. RIC did not alter the surface expression of SDF-1α on platelets.

Conclusions Despite our previous finding of increased total SDF-1α after RIC, we found no change of either total or active SDF-1α or MIF after RIC in the present murine study. This may relate to tissue oxygenation and requires further investigation. Active SDF-1α was unexpectedly decreased after RIC in humans. The implications for the role of these two chemokines in RIC still require definition.

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