If (1) 3-hydroxy-3-methylglutaryl-coenzyme reductase inhibitors (statins) block the rate-limiting step in cholesterol synthesis and promote the expression of low-density lipoprotein receptors, (2) “Gram-negative sepsis” results from an abundant systemic response to bacterial lipopolysaccharide (endotoxin), (3) triglyceride-rich lipoproteins can bind endotoxin and low-density lipoprotein receptors enhance the uptake of both of these molecules, and (4) low-density lipoprotein receptor internalization of lipoproteins and endotoxin co-opts a common transcriptional regulatory system (NF-κB) that results in reduced cell vulnerability to inflammation, then statins, in addition to their lipid-lowering capacity, enhance endotoxin clearance from the circulation and attenuate the septic response.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Surgery
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Simvastatin blunts endotoxin-induced tissue factor in vivo.Circulation. 2005; 111: 1841-1846
- The effect of statins on mortality in patients with bacteremia.Clin Infect Dis. 2001; 33: 1352-1357
- cDNA cloning of the bovine low density lipoprotein receptor.Proc Natl Acad Sci USA. 1983; 80: 7501-7505
- Relative induction of mRNA for HMG CoA reductase and LDL receptor by five different HMG-CoA reductase inhibitors in cultured human cells.J Atheroscler Thromb. 2000; 7: 138-144
- Effect of statins on lipoprotein receptor expression in cell lines from human mast cells and basophils.Eur J Clin Pharmacol. 2003; 59: 507-516
- Upregulation of the low density lipoprotein receptor at the blood-brain barrier.J Cell Biol. 1994; 126: 465-473
- Bacterial lipopolysaccharide activates NF-κB through Toll-like receptor 4 (TLR-4) in cultured human dermal endothelial cells.J Biol Chem. 2000; 275: 11058-11063
- Separate functional domains of human MD-2 mediate toll-like receptor 4 binding and lipopolysaccharide responsiveness.J Immunol. 2003; 171: 5272-5276
- Role of hepatocytes in direct clearance of lipopolysaccharide in rats.Gastroenterology. 1995; 109: 1969-1976
- Sepsis increases endocytosis of endotoxin into hepatocytes.Surgery. 1996; 120: 389-394
- Chylomicrons alter the fate of endotoxin, decreasing tumor necrosis factor release and preventing death.J Clin Invest. 1993; 91: 1028-1034
- Induction of cytokine tolerance in rodent hepatocytes by chylomicron-bound LPS is low-density lipoprotein receptor dependent.Shock. 2003; 19: 157-162
- Chylomicron-bound endotoxin selectively inhibits NF-κB activation in rat hepatocytes.Shock. 2002; 18: 182-188
- Human very low density lipoproteins and chylomicrons can protect against endotoxin-induced death in mice.J Clin Invest. 1990; 86: 696-702
Accepted: August 23, 2005San Francisco, Calif
© 2006 Mosby, Inc. Published by Elsevier Inc. All rights reserved.