Aging exacerbates microvascular endothelial damage induced by circulating factors present in the serum of septic patients

Zsuzsanna Tucsek, Tripti Gautam, William E. Sonntag, Peter Toth, Hiroshi Saito, Reinaldo Salomao, Csaba Szabo, Anna Csiszar, Zoltan Ungvari

    Research output: Contribution to journalArticle

    28 Scopus citations

    Abstract

    The elderly patients show a significantly elevated mortality rate during sepsis than younger patients, due to their higher propensity to microvascular dysfunction and consequential multiorgan 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 months) and aged (24 months) Fischer 344 × Brown Norway rats were treated with sera obtained from sepsis patients and healthy controls. Oxidative stress (MitoSox fluorescence), death receptor activation (caspase 8 activity), and apoptotic cell death (caspase 3 activity) induced by treatment with septic sera were exacerbated in aged endothelial cells as compared with responses obtained in young cells. Induction of heme oxygenase-1 and thrombomodulin in response to treatment with septic sera was impaired in aged endothelial cells. Treatment with septic sera elicited greater increases in tumor necrosis factor-expression in aged endothelial cells, as compared with young cells, whereas induction of inducible nitric oxide synthase, intercellular adhesion molecule-1, and vascular cell adhesion molecule did not differ between the two groups. Collectively, aging increases sensitivity of microvascular endothelial cells (MVECs) to oxidative stress and cellular damage induced by inflammatory factors present in the circulation during septicemia. We hypothesize that these responses may contribute to the increased vulnerability of elderly patients to multiorgan failure associated with sepsis.

    Original languageEnglish (US)
    Pages (from-to)652-660
    Number of pages9
    JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
    Volume68
    Issue number6
    DOIs
    StatePublished - Jun 1 2013

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    Keywords

    • Aging
    • Bacteremia
    • Endothelial cells
    • Microcirculation
    • Microvascular injury
    • Sepsis
    • Septic shock
    • Septicemia

    ASJC Scopus subject areas

    • Aging
    • Geriatrics and Gerontology

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