title: Resveratrol attenuates microvascular inflammation in sepsis via SIRT-1-Induced modulation of adhesion molecules in ob/ob mice.
abstract: OBJECTIVE
  Obesity, a sirtuin-1 (SIRT-1) -deficient state, increases morbidity and resource utilization in critically ill patients. SIRT-1 deficiency increases microvascular inflammation and mortality in early sepsis. The objective of the study was to study the effect of resveratrol (RSV), a SIRT-1 activator, on microvascular inflammation in obese septic mice.
  
  
  METHODS
  ob/ob and C57Bl/6 (WT) mice were pretreated with RSV versus dimethyl sulfoxide (DMSO) (vehicle) prior to cecal ligation and puncture (sepsis). We studied (1) leukocyte/platelet adhesion, (2) E-selectin, ICAM-1, and SIRT-1 expression in small intestine, and (3) 7-day survival. A group of RSV-treated mice received SIRT-1 inhibitor (EX-527) with sepsis induction, and leukocyte/platelet adhesion and E-selectin/ICAM-1 expression were studied. We treated endothelial (HUVEC) cells with RSV to study E-selectin/ICAM-1 and p65-acetylation (AC-p65) in response to lipopolysaccharide (LPS).
  
  
  RESULTS
  RSV treatment decreased leukocyte/platelet adhesion and E-selectin/ICAM-1 expression with increased SIRT-1 expression in septic ob/ob and WT mice, decreased E-selectin/ICAM-1 expression via increased SIRT-1 expression, and decreased AC-p65 expression in HUVEC. EX-527 abolished RSV-induced attenuation of microvascular inflammation in ob/ob septic mice. Finally, ob/ob mice in the sepsis+RSV group had significantly increased 7-day survival versus the sepsis+vehicle group.
  
  
  CONCLUSIONS
  RSV increases SIRT-1 expression in ob/ob septic mice to reduce microvascular inflammation and improves survival.
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Xianfeng
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.|Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Buechler
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.|Department of Surgery, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Barbara K
authors.initials: BK
authors.lastname: Yoza
authors.affiliation: Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Charles E
authors.initials: CE
authors.lastname: McCall
authors.affiliation: Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.|Department of Internal Medicine, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
authors.forename: Vidula T
authors.initials: VT
authors.lastname: Vachharajani
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000494:pharmacology*; D002432:Cecum / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D005260:Female; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism*; D018799:Intercellular Adhesion Molecule-1; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D009765:Obesity / Q000378:metabolism; D010973:Platelet Adhesiveness / Q000187:drug effects; D000077185:Resveratrol; D018805:Sepsis / Q000188:drug therapy / Q000378:metabolism*; D056564:Sirtuin 1 / Q000378:metabolism*; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D015815:Cell Adhesion Molecules; D013267:Stilbenes; D018799:Intercellular Adhesion Molecule-1; D056564:Sirtuin 1; D000077185:Resveratrol