Stimulation of cGMP signalling protects coronary endothelium against reperfusion-induced intercellular gap formation.

Aims: Ischaemia-reperfusion provokes barrier failure of the coronary microvasculature, impeding functional recovery of the heart during reperfusion. The aim of the present study was to investigate whether the stimulation of cGMP signalling by activation of soluble guanylyl cyclase (sGC) can reduce reperfusion-induced endothelial intercellular gap formation and to determine whether this is due to an influence on endothelial cytosolic Ca(2+) homeostasis during reperfusion.

Methods And Results: Experiments were performed with cultured coronary endothelial monolayers and isolated saline-perfused rat hearts.

Cytosolic Ca2+ oscillations in human cerebrovascular endothelial cells after subarachnoid hemorrhage.

Molecular mechanisms of cerebral vasospasm after subarachnoid hemorrhage (SAH) include specific modes of cell signaling like activation of nuclear factor (NF)-kappaB and vascular cell adhesion molecules (VCAM)-1 expression. The study's hypothesis is that cisternal cerebral spinal fluid (CSF) from patients after SAH may cause Ca(2+) oscillations which induce these modes of vascular inflammation in an in vitro model of human cerebral endothelial cells (HCECs). HCECs were incubated with cisternal CSF from 10 SAH patients with confirmed cerebral vasospasm.

The role of poly(ADP-ribose) polymerase (PARP) in the autonomous proliferative response of endothelial cells to hypoxia.

Objective: The autonomous proliferative response of endothelial cells to hypoxia has been shown to be dependent on activation of NAD(P)H oxidase, on the cytosolic Ca2+ load, and, consequently, on nuclear translocation of extracellular signal-regulated kinase (ERK)1/2 during transient hypoxia. The aim of the present study was to investigate whether poly(ADP-ribose) polymerase (PARP) is a downstream signal of NAD(P)H oxidase, mediating cytosolic Ca2+ load and hence nuclear translocation of ERK1/2 and endothelial cell proliferation.

Methods: Porcine aortic endothelial cells were incubated under hypoxic conditions for 40 min.

Insulin protects cardiomyocytes against reoxygenation-induced hypercontracture by a survival pathway targeting SR Ca2+ storage.

Objective: Experimental and clinical studies have shown that administration of insulin during reperfusion is cardioprotective, but the underlying mechanisms are still unknown. In this study, we investigated in isolated rat cardiomyocytes subjected to hypoxia and reoxygenation whether administration of insulin during reoxygenation reduces reoxygenation-induced hypercontracture, a hallmark of acute reperfusion injury. The effects of insulin on potential pro-survival kinases, i.