A biomimetic shock model on the effect of endothelial aging on vascular barrier properties

Aging is characterized by a decline in cellular function, which has an adverse effect on the biologic response to injury. Both aging and trauma/hemorrhagic shock (T/HS) increase oxidative stress which impairs the vascular endothelium (EC) and glycocalyx (EG). The additive effect of aging on EC and EG damage following T/HS are unknown. This was studied in an in vitro model.

Confluent endothelial cell monolayers from primary aortic endothelial cells from 10-week-old mice ("young" cells) or primary aortic cells from 65-week-old mice ("aged" cells) were established in microfluidic devices (MFDs) and perfused at constant shear conditions overnight. Mouse endothelial cell monolayers were then exposed to hypoxia/reoxygenation alone and/or epinephrine or norepinephrine. Endothelial glycocalyx degradation was indexed as well as subsequent endothelial injury/activation.

Aged endothelial cells showed increase glycocalyx shedding and subsequent loss of glycocalyx thickness. This lead to a more pronounced level of EC injury/activation compared with young endothelial cells. Although exposure to biomimetic shock conditions exacerbated both endothelial glycocalyx shedding and endothelial injury in both aged and young endothelial cells, the effect was significantly more pronounced in aged cells.

Advanced age is associated with worse outcomes in severely injured trauma patients. Our study demonstrates that there is increased EG shedding and a diminished EG layer in aged compared to "young" endothelial cell layers. Biomimetic shock conditions lead to an even greater impairment of the endothelial glycocalyx in aged versus young endothelial cell monolayers. It appears that these effects are a consequence of aging related oxidative stress at both baseline and shock conditions. This exacerbates shock-induced endotheliopathy and may contribute to untoward effects on patient outcomes in this population.