Role of Bacterial Endotoxin in Chronic Heart Failure

Abstract

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 LPS 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.

The profile of cardiovascular risk factors in heart failure obese patients hospitalised in a rehabilitation romanian hospital

“…Windler and al. showed that heart failure patients with lower total-cholestreol levels (163.6 mg/dl) have a higher mortality rate compared to those with higher total-cholesterol values (218 mg/dl) [16]. There are several pathways leading to altered cholesterol metabolism in heart failure patients, such as congestive hepatopathy, excessive proinflammatory cytokine synthesis or increased endotoxine activity [17][18][19].…”

The Impact of Antihypertensive Drug Therapy on Endotoxemia in Elderly Patients with Chronic Kidney Disease

“…Endotoxemia is associated with a wide range of well recognized pathophysiological processes; it is a profoundly proinflammatory stimulus (3) and is seen in pathologic conditions associated with malnutrition and wasting (1,2).…”

Nutrients, Nutraceuticals and Xenobiotics Affecting Renal Health

“…LPS, a component of Gram-bacterial wall, is able to promote the down-expression of tight junction proteins ZO-1 and claudin, that allow LPS to enter the bloodstream [101]. This results in a cascade of inflammatory events, including increased secretion of pro-inflammatory cytokines and chemokines, activation of macrophages and their infiltration within the renal tissues and the arterial walls, all predisposing to the development of CKD and atherosclerosis [102][103][104]. Intestinal Alkaline Phosphatase (IAP) has a very significant role in preserving mucosal barrier integrity.…”