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During the reperfusion phase, a complex interplay of multiple pathways and mechanisms is activated, which ultimately leads to cell death, primarily through apoptosis. There is some evidence from a lupus mouse model that lupus IgG, specifically the antiphospholipid (aPL) antibody subset, is pathogenic in mesenteric I\/R injury. Furthermore, it has previously been shown that the immunodominant epitope for the majority of circulating pathogenic aPLs resides in the N-terminal domain I (DI) of beta-2 glycoprotein I (<jats:italic>\u03b2<\/jats:italic><jats:sub>2<\/jats:sub>GPI). This study describes the enhanced pathogenic effect of purified IgG derived from patients with lupus and\/or the antiphospholipid syndrome in a cardiomyocyte H\/R <jats:italic>in vitro<\/jats:italic> model. Furthermore, we have demonstrated a pathogenic role for aPL containing samples, mediated via aPL\u2013<jats:italic>\u03b2<\/jats:italic><jats:sub>2<\/jats:sub>GPI interactions, resulting in activation of the pro-apoptotic p38 MAPK pathway. This was shown to be inhibited using a recombinant human peptide of domain I of <jats:italic>\u03b2<\/jats:italic><jats:sub>2<\/jats:sub>GPI in the fluid phase, suggesting that the pathogenic anti-<jats:italic>\u03b2<\/jats:italic><jats:sub>2<\/jats:sub>GPI antibodies in this <jats:italic>in vitro<\/jats:italic> model target this domain.<\/jats:p>","DOI":"10.1038\/cddis.2016.235","type":"journal-article","created":{"date-parts":[[2017,1,12]],"date-time":"2017-01-12T13:47:21Z","timestamp":1484228841000},"page":"e2549-e2549","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Antiphospholipid antibodies enhance rat neonatal cardiomyocyte apoptosis in an in vitro hypoxia\/reoxygenation injury model via p38 MAPK"],"prefix":"10.1038","volume":"8","author":[{"given":"Lauren T","family":"Bourke","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"McDonnell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James","family":"McCormick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charis","family":"Pericleous","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vera M","family":"Ripoll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ian","family":"Giles","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anisur","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasis","family":"Stephanou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yiannis","family":"Ioannou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,1,12]]},"reference":[{"key":"BFcddis2016235_CR1","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1111\/j.1538-7836.2006.01753.x","volume":"4","author":"S Miyakis","year":"2006","unstructured":"Miyakis S, Lockshin MD, Atsumi T, Branch DW, Brey RL, Cervera R et al. 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