Seal Endothelial Cells: a Comparative Model to Study Natural Tolerance to Ischemia/Reperfusion

• Published in: The FASEB Journal
• Main Authors: Vazquez‐Medina, Jose Pablo, Allen, Kaitlin, Hindle, Allyson G.
• Format: Article in Journal/Newspaper
• Language: English
• Published: Wiley 2018
• Subjects: Weddell; Weddell Seal
• Online Access: http://dx.doi.org/10.1096/fasebj.2018.32.1_supplement.859.8

Reperfusion injury is a common complication derived from ischemia/reperfusion events that occur in the course of myocardial infarction, stroke, embolism and other peripheral vascular diseases. Lack of blood during ischemic episodes activates cellular pathways that upregulate pro‐inflammatory signaling and increase oxidant generation. Reperfusion after ischemia leads to the recruitment of inflammatory cells further exacerbating oxidant production and ultimately resulting in cell death, tissue injury and organ dysfunction. Seals experience routine, repetitive episodes of peripheral ischemia/reperfusion during and after dives. These ischemia/reperfusion events are a direct consequence of the cardiovascular adjustments that allow seals to maximize the use of their oxygen stores while diving but result in selectively reduced perfusion to peripheral tissues. Remarkably, seals show no apparent detrimental effects associated with these ischemia/reperfusion events. The cellular mechanisms that underlie this natural tolerance to a potentially pathological condition, however, remain unknown. We isolated and cryopreserved primary endothelial cells from Weddell seal placental arteries to study the mechanisms that confer ischemic tolerance to seal cells. Seal endothelial cells were evaluated for dil‐acetylated low‐density lipoprotein (dil‐AcLDL) uptake and immunostained with endothelial markers to confirm the endothelial phenotype of the preparation. Seal cells were also stimulated with phorbol ester to test whether or not they are capable of producing oxidants. Weddell seal endothelial cell monolayers exhibit a cobblestone‐like morphology characteristic of human and murine endothelial cells and stained positive for vascular endothelial cadherin by immunofluorescence. Live seal cells in culture were functionally capable of incorporating labeled dil‐AcLDL and generated hydrogen peroxide in a concentration‐dependent manner when stimulated with phorbol ester. These results suggest that primary seal endothelial cells in culture ...