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 language | English |
|---|---|
| Pages (from-to) | 652-660 |
| Number of pages | 9 |
| Journal | Journals of Gerontology - Series A Biological Sciences and Medical Sciences |
| Volume | 68 |
| Issue number | 6 |
| DOIs | |
| State | Published - Jun 2013 |
Bibliographical note
Funding Information:Funding This work was supported by grants from the American Heart Association (to Z.U., P.T., and A.C.), American Federation for Aging Research (to A.C.), the Oklahoma Center for the Advancement of Science and Technology (to A.C. and Z.U.), the National Institutes of Health (AG031085 to A.C.; AT006526 to Z.U.; AG038747, NS056218, and P01 AG11370 to W.E.S.), the Ellison Medical Foundation and the Arkansas Claude Pepper Older Americans Independence Center at University of Arkansas Medical Center (to A.C.), and the American Diabetes Association (to C.S.). The authors would like to express their gratitude for the support of the Donald W. Reynolds Foundation, which funds aging research at the University of Oklahoma Health Sciences Center under its Aging and Quality of Life Program.
Funding
Funding This work was supported by grants from the American Heart Association (to Z.U., P.T., and A.C.), American Federation for Aging Research (to A.C.), the Oklahoma Center for the Advancement of Science and Technology (to A.C. and Z.U.), the National Institutes of Health (AG031085 to A.C.; AT006526 to Z.U.; AG038747, NS056218, and P01 AG11370 to W.E.S.), the Ellison Medical Foundation and the Arkansas Claude Pepper Older Americans Independence Center at University of Arkansas Medical Center (to A.C.), and the American Diabetes Association (to C.S.). The authors would like to express their gratitude for the support of the Donald W. Reynolds Foundation, which funds aging research at the University of Oklahoma Health Sciences Center under its Aging and Quality of Life Program.
| Funders | Funder number |
|---|---|
| Arkansas for Medical Sciences’ General Clinical Research Center | |
| National Institutes of Health (NIH) | AG031085, AG038747, P01 AG11370, AT006526 |
| National Institutes of Health (NIH) | |
| American Diabetes Association Inc | |
| Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council | R01NS056218 |
| Institute of Neurological Disorders and Stroke National Advisory Neurological Disorders and Stroke Council | |
| Ellison Medical Foundation | |
| Donald W. Reynolds Foundation | |
| American Federation for Aging Research | |
| American the American Heart Association | |
| University Oklahoma Health Sciences Center | |
| Claude Pepper Older Americans Independence Center, Wake Forest School of Medicine | |
| Oklahoma Center for the Advancement of Science and Technology |
Keywords
- Aging
- Bacteremia
- Endothelial cells
- Microcirculation
- Microvascular injury
- Sepsis
- Septic shock
- Septicemia
ASJC Scopus subject areas
- General Medicine