Role of bacterial endotoxin in chronic heart failure: The gut of the matter.
15 - 23.
Proinflammatory cytokines are now thought to play a key role in the pathophysiology of chronic heart failure, driving both symptomatic presentation and disease progression. We propose that this proinflammatory state, in turn, may be sustained through a chronic release of enterically derived bacterial endotoxin. Human trials have indicated that bacterial decontamination of the gut with concomitant decrease in lipopolysaccharide (LPS) has a positive outcome on heart disease patients. Antiendotoxin antibodies may thus represent therapeutic agents in this setting. Previously, antiendotoxin antibodies were targeted to the inner hydrophobic lipid A moiety of endotoxin in an attempt to neutralize its toxicity. These antibodies failed because they lacked specificity and bound to LIDS weakly. In contrast, our studies on antiendotoxin antibodies have revealed that antibodies targeted to the hydrophilic oligosaccharides of the endotoxin have the potential to bind specifically with high affinity. Development of immunotherapeutics that can reduce systemic LPS or other agents, such as bactericidal/permeability-increasing protein that can neutralize LPS and limit inflammation safely, will enable the role of LPS in chronic heart failure to be elucidated and may pave the way to develop a new generation of effective therapeutic agents that may be directed to the treatment of chronic heart failure.
|Title:||Role of bacterial endotoxin in chronic heart failure: The gut of the matter|
|Keywords:||antibodies, hypoxia, inflammation, interleukins, nitric oxide, pathology, E. coli, endotoxin, TUMOR-NECROSIS-FACTOR, BACTERICIDAL/PERMEABILITY-INCREASING PROTEIN, NITRIC-OXIDE SYNTHASE, LIPOPOLYSACCHARIDE (LPS)-BINDING PROTEIN, IDIOPATHIC DILATED CARDIOMYOPATHY, GRAM-NEGATIVE BACTERIA, TOLL-LIKE RECEPTOR-4, MYOCARDIAL OXYGEN-CONSUMPTION, ANTIENDOTOXIN CORE ANTIBODIES, ISCHEMIA-REPERFUSION INJURY|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Medicine (Division of) > Clinical Physiology
UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of)
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