Pathologically elevated cyclic hydrostatic pressure induces CD95-mediated apoptotic cell death in vascular endothelial cells

Abstract

We describe cyclic hydrostatic pressure of 200/100 mmHg with a frequency of 85/min as a hemodynamically relevant pathological condition enforcing apoptosis in endothelial cells (EC) after 24 h of treatment. This went along with an increase of CD95 and CD95L surface expression, shedding of CD95L into the supernatant, cleavage of caspase-3 and caspase-8, and elevated JNK-2, c-Jun, and CD95L mRNA expression. Furthermore, increased DNA-binding activity of the AP-1 transcription factor family members FRA-1 and c-Jun was observed. This activation was reduced by inhibition of JNK, which subsequently prevented elevated CD95L mRNA expression. Caspase inhibitors and a CD95L-neutralizing antibody also reduced EC apoptosis. Most of the pressure-induced events were most prominent at 24 and 48 h. However, after 48 h, the CD95/CD95L expression pattern switched back to CD95-/CD95L+ and the specific death rate decreased. Cyclic pathological hydrostatic pressure is a novel type of stress to EC that renders them susceptible to CD95/CD95L-mediated autoapoptosis and/or paracrine apoptosis accompanied by upregulation of intracellular molecules known to trigger both apoptosis and survival.

Induction of chondrogenic phenotype in synovium-derived progenitor cells by intermittent hydrostatic pressure

“…These findings suggest that IHP-induced cartilage differentiation by SPCs may be mediated by the JNK pathway. A previous study of vascular endothelial cells showed that the JNK pathway is involved in signal transduction for IHP and in increased expression of c-Jun 73 . The present study is the first to report mechanisms for cartilage differentiation via increased expressions of c-Jun and SOX-9 by SPCs after exposure to IHP.…”

Regulation of Epithelial Cell Functions by the Osmolality and Hydrostatic Pressure Gradients: A Possible Role of the Tight Junction as a Sensor

“…There are many reports which show that the HP from apical or the basal side affects various endothelial functions such as transendothelial transport, cell adhesion, cell shape, intracellular Ca 2+ concentration, expression of cytokines and so on [64,65,66,67,68,69,70,71,72]. On the other hand, the increase of 50–270 cmH 2 O HP to the whole cell by using specialized pressure chamber also affects various endothelial functions including transendothelial electrical resistance, cytoskeletons, cell proliferation, and expression of cytokines and cell adhesion proteins [73,74,75,76,77]. Furthermore, smaller HP (2 to 27 cmH 2 O) is also shown to have effects on F-actin and cell proliferation [78,79,80,81], although there is a report which shows that 136 cmH 2 O HP has no effect on F-actin and cell proliferation in endothelia [82].…”

Evidence of Notch pathway activation in the ectatic ducts of chronic pancreatitis

“…HPDE cells were placed in a previously described pressurized chamber based on the Flexcell Strain Unit and subjected to a sustained pressure of 200 mmHg for 24 h 17, 18. In short, the pressurized chamber enables the exertion of sustained pressure on cells in vitro , with a dynamic airflow and a defined membrane extension regulated by spacers.…”

“…In short, the pressurized chamber enables the exertion of sustained pressure on cells in vitro , with a dynamic airflow and a defined membrane extension regulated by spacers. During operation up to 220 mmHg, O 2 partial pressures and pH in the cell culture medium do not change compared to control cultures kept at normal atmosphere 17, 18. HPDE cells kept under identical culture conditions without pressure were used as controls.…”