Systemic inflammation has been suggested to have a pivotal role in atherothrombosis, but the factors that trigger systemic inflammation have not been fully elucidated. Lipopolysaccharide (LPS) is a component of the membrane of Gram-negative bacteria present in the gut that can translocate into the systemic circulation, causing non-septic, low-grade endotoxaemia. Gut dysbiosis is a major determinant of low-grade endotoxaemia via dysfunction of the intestinal barrier scaffold, which is a prerequisite for LPS translocation into the systemic circulation. Experimental studies have demonstrated that LPS is present in atherosclerotic arteries but not in normal arteries. In atherosclerotic plaques, LPS promotes a pro-inflammatory status that can lead to plaque instability and thrombus formation. Low-grade endotoxaemia affects several cell types, including leukocytes, platelets and endothelial cells, leading to inflammation and clot formation. Low-grade endotoxaemia has been described in patients at risk of or with overt cardiovascular disease, in whom low-grade endotoxaemia was associated with atherosclerotic burden and its clinical sequelae. In this Review, we describe the mechanisms favouring the development of low-grade endotoxaemia, focusing on gut dysbiosis and changes in gut permeability; the plausible biological mechanisms linking low-grade endotoxaemia and atherothrombosis; the clinical studies suggesting that low-grade endotoxaemia is a risk factor for cardiovascular events; and the potential therapeutic tools to improve gut permeability and eventually eliminate low-grade endotoxaemia.

Gut-derived low-grade endotoxaemia, atherothrombosis and cardiovascular disease / Violi, Francesco; Cammisotto, Vittoria; Bartimoccia, Simona; Pignatelli, Pasquale; Carnevale, Roberto; Nocella, Cristina. - In: NATURE REVIEWS. CARDIOLOGY. - ISSN 1759-5002. - (2022). [10.1038/s41569-022-00737-2]

Gut-derived low-grade endotoxaemia, atherothrombosis and cardiovascular disease

Francesco Violi
Primo
;
Vittoria Cammisotto;Simona Bartimoccia;Pasquale Pignatelli;Roberto Carnevale;Cristina Nocella
Ultimo
2022

Abstract

Systemic inflammation has been suggested to have a pivotal role in atherothrombosis, but the factors that trigger systemic inflammation have not been fully elucidated. Lipopolysaccharide (LPS) is a component of the membrane of Gram-negative bacteria present in the gut that can translocate into the systemic circulation, causing non-septic, low-grade endotoxaemia. Gut dysbiosis is a major determinant of low-grade endotoxaemia via dysfunction of the intestinal barrier scaffold, which is a prerequisite for LPS translocation into the systemic circulation. Experimental studies have demonstrated that LPS is present in atherosclerotic arteries but not in normal arteries. In atherosclerotic plaques, LPS promotes a pro-inflammatory status that can lead to plaque instability and thrombus formation. Low-grade endotoxaemia affects several cell types, including leukocytes, platelets and endothelial cells, leading to inflammation and clot formation. Low-grade endotoxaemia has been described in patients at risk of or with overt cardiovascular disease, in whom low-grade endotoxaemia was associated with atherosclerotic burden and its clinical sequelae. In this Review, we describe the mechanisms favouring the development of low-grade endotoxaemia, focusing on gut dysbiosis and changes in gut permeability; the plausible biological mechanisms linking low-grade endotoxaemia and atherothrombosis; the clinical studies suggesting that low-grade endotoxaemia is a risk factor for cardiovascular events; and the potential therapeutic tools to improve gut permeability and eventually eliminate low-grade endotoxaemia.
2022
Microbiota, Thrombosi
01 Pubblicazione su rivista::01d Recensione
Gut-derived low-grade endotoxaemia, atherothrombosis and cardiovascular disease / Violi, Francesco; Cammisotto, Vittoria; Bartimoccia, Simona; Pignatelli, Pasquale; Carnevale, Roberto; Nocella, Cristina. - In: NATURE REVIEWS. CARDIOLOGY. - ISSN 1759-5002. - (2022). [10.1038/s41569-022-00737-2]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1667560
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