Antiphospholipid antibodies enhance rat neonatal cardiomyocyte apoptosis in an in vitro hypoxia/reoxygenation injury model via p38 MAPK

Abstract

A significant amount of myocardial damage during a myocardial infarction (MI) occurs during the reperfusion stage, termed ischaemia/reperfusion (I/R) injury, and accounts for up to 50% of total infarcted tissue post-MI. 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 (β2GPI). 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 in vitro model. Furthermore, we have demonstrated a pathogenic role for aPL containing samples, mediated via aPL–β2GPI 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 β2GPI in the fluid phase, suggesting that the pathogenic anti-β2GPI antibodies in this in vitro model target this domain.

Escin induces caspase-dependent apoptosis and autophagy through the ROS/p38 MAPK signalling pathway in human osteosarcoma cells in vitro and in vivo

“…The activated MAPK signalling pathway can induce cell death in cancer. 39 Thus, we explored whether this pathway is activated by escin in osteosarcoma. The expression levels of p38, JNK and ERK-2 were determined by western blot analysis.…”

miR‑155 inhibition represents a potential valuable regulator in mitigating myocardial hypoxia/reoxygenation injury through targeting BAG5 and MAPK/JNK signaling

“…It has been suggested that the JNK/MAPK signaling pathway is associated with various pathophysiological processes during apoptosis and oxidative stress. Bourke et al (50) demonstrated that, in an in vitro H/r injury model, anti-phospholipid antibodies enhanced the levels of apoptosis of newborn rat cardiac myocytes through p38 MAPK. It has previously been observed that myocardial cells were protected from H/r injury through inhibiting JNK (51).…”

Antibodies against TFPI and protein C are associated with a severe thrombotic phenotype in patients with and without antiphospholipid syndrome

“…previously described ones (34)(35)(36) with slight modifications. Patient plasma samples diluted to a 50% maximal binding dose and were incubated with either protein C or β2GP1 (0-2.5µM) for 2 hours and subsequently added in duplicate into an ELISA plate coated with β2GPI for 1 hour at room temperature before washed with PBST.…”