APOE polymorphism is associated with risk of severe sepsis in surgical patients*

Moretti, Eugene W.; Morris, Richard; Podgoreanu, Mihai V.; Schwinn, Debra A.; Newman, Mark F.; Bennett, Ellen; Moulin, Victor G.; Uzo, U; Laskowitz, Daniel T.

doi:10.1097/01.ccm.0000186368.96146.fb

Cited by 54 publications

(30 citation statements)

References 59 publications

(56 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…ApoE also plays a role in antigen presentation to natural killer T-cells by transporting bacterial lipids to CD1 via dendritic cell LDL receptors (14). Although the impact of apoE on human immunity is poorly understood, the finding that an apoE polymorphism is associated with the risk of severe sepsis in surgical patients (15) supports a role for apoE in human host defense.…”

mentioning

confidence: 92%

Infection induces a positive acute phase apolipoprotein E response from a negative acute phase gene: role of hepatic LDL receptors*

Thompson

Kitchens

2008

Journal of Lipid Research

View full text Add to dashboard Cite

Apolipoprotein E (apoE) plays important roles in lipid homeostasis, anti-inflammation, and host defense. Since tissue apoE mRNA levels have been reported to decrease during inflammatory responses, we were surprised to find that plasma apoE levels were significantly elevated during septic infections in both humans and mice. This apparent paradox was also observed during lipopolysaccharideinduced acute inflammation in mice: plasma levels of apoE increased up to 4-fold despite sharply decreased apoE gene expression in the liver, macrophages, and extrahepatic tissues. We hypothesized that apoE levels were augmented by decreased plasma clearance. Our analysis revealed that apoE associated principally with HDL in mice and that apoE was cleared from the circulation principally via LDL receptors. The acute inflammatory response decreased LDL receptor expression in the liver and significantly reduced the rate of apoE clearance. In contrast, the same inflammatory stimuli increased LDL receptor expression in macrophages. Our results define a novel acute phase mechanism that increases circulating apoE levels as apoE production decreases. Diminished hepatic LDL receptor expression may thus cooperate with elevated LDL receptor expression in macrophages to facilitate the forward transport of apoE and its associated lipids to these key defense cells.

show abstract

mentioning

confidence: 92%

Infection induces a positive acute phase apolipoprotein E response from a negative acute phase gene: role of hepatic LDL receptors*

Thompson

Kitchens

2008

Journal of Lipid Research

View full text Add to dashboard Cite

show abstract

“…Earlier, it was shown that, among the 22mer helices of apoA-I, only the N-and C-terminal helices were able to associate with phospholipids while the other regions (either effects of the apolipoprotein are independent of its cholesterol-lowering property (99)(100)(101)(102). Polymorphisms in the apoE gene are associated with enhancement of the infl ammatory response and an increase in mortality in animal models and patients with sepsis ( 103,104 ). Deletion of the apoE gene also induces these responses in mice treated with either bacterial lipopolysaccharide (LPS) or infected with bacterial pathogens ( 101,102,105 ).…”

Section: Clinical Evaluation Of the Apoa-i Mimetic Peptide 4fmentioning

confidence: 99%

Anti-inflammatory and cholesterol-reducing properties of apolipoprotein mimetics: a review

White

Garber

Anantharamaiah

2014

Journal of Lipid Research

View full text Add to dashboard Cite

“…27 In a cohort of 343 patients of mainly Caucasian ethnicity (83.1%), who underwent elective major non-cardiac surgery, Moretti et al found a protective effect of the Apo E3 allele with a lower incidence of severe sepsis after surgery. 20 Those links between ApoE genotypes and inflammation has led to studies that analyzed associations between ApoE genotypes with postoperative CSA-AKI.…”

Section: Apoementioning

confidence: 99%

“…19 ApoE variants influence the outcome of severe sepsis in surgical patients. 20 In the context of cardiac surgery, former studies have linked ApoE genotypes with renal failure, 5,9,21 postoperative changes in neurobehavioral status [22][23][24] and inflammation. 22,[25][26][27][28] As a pro-inflammatory cytokine, TNF plays a key role in the inflammatory response after CPB.…”

Section: Introductionmentioning

confidence: 99%

Apolipoprotein E genotype, TNF-α 308G/A and risk for cardiac surgery associated-acute kidney injury in Caucasians

et al. 2013

View full text Add to dashboard Cite

Objectives: Acute kidney injury following cardiac surgery depicts a severe clinical problem that is strongly associated with adverse short-and long-term outcome. We analyzed two common genetic polymorphisms that have previously been linked to renal failure and inflammation, and have been supposed to be associated with cardiac surgery associated-acute kidney injury (CSA-AKI). Methods: A total of 1415 consecutive patients who underwent elective cardiac surgery with CPB at our institution were prospectively enrolled. Patients were genotyped for Apolipoprotein E (ApoE E2,E3,E4) (rs429358 and rs7412) and TNF-a-308 G4A (rs1800629). Results: Demographic characteristics and procedural data revealed no significant differences between genotypes. No association between ApoE (E2,E3,E4) and TNF-a-308 G4A genotypes and the RIFLE criteria could be detected. Several multiple linear regression analyses for postoperative creatinine increase revealed highly significant associations for aortic cross clamp time (p50.001), CPB-time (p50.001), norepinephrine (p50.001), left ventricular function (p ¼ 0.004) and blood transfusion (p50.001). No associations were found for ApoE (E2,E3,E4) and TNF-a-308 G4A genotypes or baseline creatinine. When the sample size is 1415, the multiple linear regression test of R 2 ¼ 0 for seven covariates assuming normal distribution will have at least 99% power with significance level 0.05 to detect an R 2 of 0.108 or 0.107 as observed in the data. Conclusions: ApoE (E2,E3,E4) polymorphism and the TNF-a-308 G4A polymorphism are not associated with renal injury after CPB.

show abstract

APOE polymorphism is associated with risk of severe sepsis in surgical patients*

Abstract: In an elective surgical cohort, presence of the APOepsilon3 allele is associated with decreased incidence of severe sepsis and a shorter ICU length of stay.

Cited by 54 publications

References 59 publications

Infection induces a positive acute phase apolipoprotein E response from a negative acute phase gene: role of hepatic LDL receptors*

Infection induces a positive acute phase apolipoprotein E response from a negative acute phase gene: role of hepatic LDL receptors*

Anti-inflammatory and cholesterol-reducing properties of apolipoprotein mimetics: a review

Apolipoprotein E genotype, TNF-α 308G/A and risk for cardiac surgery associated-acute kidney injury in Caucasians

Contact Info

Product

Resources

About