Cardiovascular research
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Cardiovascular research · Feb 2011
Soluble FLT1 sensitizes endothelial cells to inflammatory cytokines by antagonizing VEGF receptor-mediated signalling.
Pre-eclampsia affects 5-7% of pregnancies, and is a major cause of maternal and foetal death. Elevated serum levels of placentally derived splice variants of the vascular endothelial growth factor (VEGF) receptor, soluble fms-like tyrosine kinase-1 (sFLT1), are strongly implicated in the pathogenesis but, as yet, no underlying mechanism has been described. An excessive inflammatory-like response is thought to contribute to the maternal endothelial cell dysfunction that characterizes pre-eclampsia. We hypothesized that sFLT1 antagonizes autocrine VEGF-A signalling, rendering endothelial cells more sensitive to pro-inflammatory factors also released by the placenta. We tested this by manipulating VEGF receptor signalling and treating endothelial cells with low doses of tumour necrosis factor-α (TNF-α). ⋯ Our data describe a mechanism by which sFLT1 sensitizes endothelial cells to pro-inflammatory factors, providing an explanation for how placental stress may precipitate the pre-eclamptic syndrome.
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Cardiovascular research · Feb 2011
Role of the autonomic nervous system in cardioprotection by remote preconditioning in isoflurane-anaesthetized dogs.
Remote ischaemic preconditioning (rIPC) protects cardiac and non-cardiac tissues against ischaemic injury. Although there is increased demand to investigate its potential clinical applicability, fundamental mechanisms responsible for rIPC-mediated protection remain unresolved. We examined in isoflurane-anaesthetized dogs whether an intact cardiac nervous system was necessary to mediate rIPC protection against ischaemic injury. ⋯ We report robust myocardial protection by rIPC against ischaemic injury in canines that was not abrogated by either pharmacological or surgical decentralization of cardiac nerves.