| Title: |
Effects of intra-abdominal sepsis on atherosclerosis in mice |
| Authors: |
Kaynar, AM; Yende, S; Zhu, L; Frederick, DR; Chambers, R; Burton, CL; Carter, M; Stolz, DB; Agostini, B; Gregory, AD; Nagarajan, S; Shapiro, SD; Angus, DC |
| Publication Year: |
2014 |
| Collection: |
University of Pittsburgh: D-Scholarship@Pitt |
| Description: |
Introduction: Sepsis and other infections are associated with late cardiovascular events. Although persistent inflammation is implicated, a causal relationship has not been established. We tested whether sepsis causes vascular inflammation and accelerates atherosclerosis.Methods: We performed prospective, randomized animal studies at a university research laboratory involving adult male ApoE-deficient (ApoE-/-) and young C57B/L6 wild-type (WT) mice. In the primary study conducted to determine whether sepsis accelerates atherosclerosis, we fed ApoE-/- mice (N = 46) an atherogenic diet for 4 months and then performed cecal ligation and puncture (CLP), followed by antibiotic therapy and fluid resuscitation or a sham operation. We followed mice for up to an additional 5 months and assessed atheroma in the descending aorta and root of the aorta. We also exposed 32 young WT mice to CLP or sham operation and followed them for 5 days to determine the effects of sepsis on vascular inflammation.Results: ApoE-/- mice that underwent CLP had reduced activity during the first 14 days (38% reduction compared to sham; P < 0.001) and sustained weight loss compared to the sham-operated mice (-6% versus +9% change in weight after CLP or sham surgery to 5 months; P < 0.001). Despite their weight loss, CLP mice had increased atheroma (46% by 3 months and 41% increase in aortic surface area by 5 months; P = 0.03 and P = 0.004, respectively) with increased macrophage infiltration into atheroma as assessed by immunofluorescence microscopy (0.52 relative fluorescence units (rfu) versus 0.97 rfu; P = 0.04). At 5 months, peritoneal cultures were negative; however, CLP mice had elevated serum levels of interleukin 6 (IL-6) and IL-10 (each at P < 0.05). WT mice that underwent CLP had increased expression of intercellular adhesion molecule 1 in the aortic lumen versus sham at 24 hours (P = 0.01) that persisted at 120 hours (P = 0.006). Inflammatory and adhesion genes (tumor necrosis factor α, chemokine (C-C motif) ligand 2 and ... |
| Document Type: |
article in journal/newspaper |
| File Description: |
application/pdf; text/plain |
| Language: |
English |
| ISSN: |
1364-8535 |
| Relation: |
https://d-scholarship.pitt.edu/29496/1/art%253A10.1186%252Fs13054-014-0469-1.pdf; https://d-scholarship.pitt.edu/29496/7/licence.txt; Kaynar, AM and Yende, S and Zhu, L and Frederick, DR and Chambers, R and Burton, CL and Carter, M and Stolz, DB and Agostini, B and Gregory, AD and Nagarajan, S and Shapiro, SD and Angus, DC (2014) Effects of intra-abdominal sepsis on atherosclerosis in mice. Critical Care, 18 (5). ISSN 1364-8535 |
| Availability: |
https://d-scholarship.pitt.edu/29496/ |
| Rights: |
attached |
| Accession Number: |
edsbas.FC6284AE |
| Database: |
BASE |