| First Author | Zhang P | Year | 2016 |
| Journal | PLoS One | Volume | 11 |
| Issue | 3 | Pages | e0152681 |
| PubMed ID | 27031114 | Mgi Jnum | J:248965 |
| Mgi Id | MGI:6092710 | Doi | 10.1371/journal.pone.0152681 |
| Citation | Zhang P, et al. (2016) The Fifth Domain of Beta 2 Glycoprotein I Protects from Natural IgM Mediated Cardiac Ischaemia Reperfusion Injury. PLoS One 11(3):e0152681 |
| abstractText | Reperfusion after a period of ischemia results in reperfusion injury (IRI) which involves activation of the inflammatory cascade. In cardiac IRI, IgM natural antibodies (NAb) play a prominent role through binding to altered neoepitopes expressed on damaged cells. Beta 2 Glycoprotein I (beta2GPI) is a plasma protein that binds to neoepitopes on damaged cells including anionic phospholipids through its highly conserved Domain V. Domain I of beta2GPI binds circulating IgM NAbs and may provide a link between the innate immune system, IgM NAb binding and cardiac IRI. This study was undertaken to investigate the role of Beta2GPI and its Domain V in cardiac IRI using wild-type (WT), Rag-1 -/- and beta2GPI deficient mice. Compared with control, treatment with Domain V prior to cardiac IRI prevented binding of endogenous beta2GPI to post-ischemic myocardium and resulted in smaller myocardial infarction size in both WT and beta2GPI deficient mice. Domain V treatment in WT mice also resulted in less neutrophil infiltration, less apoptosis and improved ejection fraction at 24 h. Rag-1 -/- antibody deficient mice reconstituted with IgM NAbs confirmed that Domain V prevented IgM NAb induced cardiac IRI. Domain V remained equally effective when delivered at the time of reperfusion which has therapeutic clinical relevance.Based upon this study Domain V may function as a universal inhibitor of IgM NAb binding in the setting of cardiac IRI, which offers promise as a new therapeutic strategy in the treatment of cardiac IRI. |
