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Aging exacerbates microvascular endothelial damage induced by inflammatory factors present in the circulation during sepsis
Author(s) -
Tucsek Zsuzsanna,
Gautam Tripti,
Sonntag William,
Toth Peter,
Csiszar Anna,
Saito Hiroshi,
Szabo Csaba,
Ungvari Zoltan
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.1058.11
Subject(s) - sepsis , endothelial stem cell , inflammation , oxidative stress , endothelial dysfunction , apoptosis , medicine , immunology , endothelium , endothelial activation , reactive oxygen species , programmed cell death , biology , microbiology and biotechnology , biochemistry , in vitro
The elderly show a significantly elevated mortality rate during sepsis than younger patients, due to their higher propensity to microvascular dysfunction and consequential multi‐organ failure. We tested whether aging renders vascular endothelial cells more susceptible to damage induced by inflammatory factors present in the circulation during sepsis. Primary microvascular endothelial cells derived from young (3 m.o.) and aged (24 m.o.) F344xBN rats were treated with sera obtained from sepsis patients and healthy controls. Apoptotic cell death (caspase 3 and caspase 8 activities) induced by treatment with septic sera was exacerbated in aged endothelial cells as compared to responses obtained in young cells. In aged endothelial cells, compared to young cells, DAF fluorescence, indicating NO production, was decreased both under basal conditions and after treatment with septic sera. Treatment with septic sera elicited greater increases in mitochondrial production of reactive oxygen species (MitoSox fluorescence) and NF‐kappaB activation (reporter gene assay) in aged endothelial cells, as compared to young cells. Collectively, aging increases sensitivity of microvascular endothelial cells to oxidative stress and cellular damage induced by inflammatory factors present in the circulation, which likely contributes to the increased vulnerability of elderly patients to sepsis.