Localization of lipopolysaccharide from Escherichia Coli into human atherosclerotic plaque

Abstract

Experimental studies showed that gut-derived lipopolysaccharide (LPS) is pro-atherogenic, however, its relationship with human atherosclerosis is still to be defined. We investigate if gut-derived LPS from Escherichia Coli localizes in human carotid plaque and its potential role as pro-inflammatory molecule in the atherosclerotic lesion. LPS from Escherichia Coli and Toll-like receptor 4 (TLR4) were studied in specimens from carotid and thyroid arteries of 10 patients undergoing endarterectomy and 15 controls matched for demographic and clinical characteristics. Blood LPS were significantly higher in patients compared to controls. Immunochemistry analysis revealed positivity for antibodies against LPS and TLR4 coincidentally with positivity for CD68 only in the atherosclerotic plaque of carotid arteries but not in thyroid arteries; the positivity for LPS and TLR4 was greater in the area with activated macrophages. LPS concentration similar to that detected in atherosclerotic plaque resulted in a dose-dependent TLR4-mediated Nox2 up-regulation by human monocytes. These data provide the first evidence that LPS from Escherichia Coli localizes in human plaque and may contribute to atherosclerotic damage via TLR4-mediated oxidative stress.

Contribution of the commensal microbiota to atherosclerosis and arterial thrombosis

“…Epidemiological studies on carotid artery atherosclerosis (Kiechl et al ., ) and various animal models (Björkbacka et al ., ) established that innate immune receptor signalling is an important determinant of atherogenesis. Furthermore, in hypertensive endarterectomy patients, blood LPS levels were significantly elevated, and macrophages in atherosclerotic plaque specimens and carotid arteries stained positive for LPS (Carnevale et al ., ). Demonstrating the functional involvement of LPS, the intravenously administered TLR4 agonist LPS from Escherichia coli accelerated the formation of atherosclerotic lesions, in a hypercholesterolemic rabbit model, as evaluated by increased lesion size, lesion thickness and lesion volume (Lehr et al ., ).…”

The Gut Microbiota in Cardiovascular Disease and Arterial Thrombosis

“…There is increasing evidence for the gut microbiota as a relevant source of MAMPs, contributing to low but metabolically active levels of these molecules in the bloodstream [21,73]. Dependent on gut barrier function, these blood-borne MAMPs may contribute to remote signaling in distant organs [21,74] and promote chronic inflammatory processes, such as white adipose tissue inflammation, atherosclerosis, and cerebral cavernous malformations [11,[74][75][76]. The presence of a gut microbiota, constantly challenging the host, drives the expression of inflammatory mediators, which then recruit immune cells.…”

Oxidative stress and gut-derived lipopolysaccharides in children affected by Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections.

“…Lipopolysaccharide (LPS), derived from gram-negative bacteria, plays a pivotal role in causing neuroinflammation by an increase of oxidative stress [12,15,16]. A relationship among LPS, oxidative stress and NOX2 activation, in other clinical situations as NAFLD [17], pneumonia [18] atherosclerosis [19] and neurodegenerative disease [16], has been previously reported. We speculated that children affected by PANDAS have NOX2 over-activation and increased oxidative stress that may contribute to onset and persistence of the disease.…”