Helicobacter pylori Infection Acts Synergistically with a High-Fat Diet in the Development of a Proinflammatory and Potentially Proatherogenic Endothelial Cell Environment in an Experimental Model

Abstract

Classic atherosclerosis risk factors do not explain all cases of chronic heart disease. There is significant evidence that gut microbiota may influence the development of atherosclerosis. The widespread prevalence of chronic Helicobacter pylori (H. pylori, HP) infections suggests that HP can be the source of components that stimulate local and systemic inflammatory responses. Elevated production of reactive oxygen species during HP infection leads to cholesterol oxidation, which drives atherogenesis. The aim of this study is to explore the link between persistent HP infection and a high-fat diet in the development of proinflammatory conditions that are potentially proatherogenic. An in vivo model of Caviae porcellus infected with HP and exposed to an experimental diet was investigated for the occurrence of a proinflammatory and proatherogenic endothelial environment. Vascular endothelial primary cells exposed to HP components were tested in vitro for oxidative stress, cell activation and apoptosis. The infiltration of inflammatory cells into the vascular endothelium of animals infected with HP and exposed to a high-fat diet was observed in conjunction with an increased level of inflammatory markers systemically. The arteries of such animals were the least elastic, suggesting the role of HP in arterial stiffness. Soluble HP components induced transformation of macrophages to foam cells in vitro and influenced the endothelial life span, which was correlated with Collagen I upregulation. These preliminary results support the hypothesis that HP antigens act synergistically with a high-fat diet in the development of proatherogenic conditions.

Accumulation of Deleterious Effects in Gastric Epithelial Cells and Vascular Endothelial Cells In Vitro in the Milieu of Helicobacter pylori Components, 7-Ketocholesterol and Acetylsalicylic Acid

“…In addition, the presence of soluble immune complexes containing H. pylori antigens in the sera of CHD patients might reflect the systemic effects of H. pylori infection that are related to an increased inflammatory response in the vascular endothelium [ 13 ]. It has been shown that Caviae porcellus infected experimentally with H. pylori had more severe peripheral arterial stiffness compared to those non-infected [ 7 ].…”

“…By using the cell cultures of the primary gastric epithelial cells and fibroblasts of these animals, it was revealed that an increased amount of ROS was followed by an elevated rate of apoptosis, an upregulation of both the local and systemic metalloproteinase (MMP)-9 concentrations, and diminished cell integrity [ 9 , 10 ]. Recently, Krupa et al (2021) [ 30 ] showed that vascular endothelial cells are sensitive to H. pylori antigenic signals, which may initiate apoptosis in conjunction with an upregulation of MMP-9 [ 7 ]. It is possible that during infection with H. pylori both ROS and MMP-9-driven apoptosis may be involved in atherogenesis [ 30 ].…”

“…The direct interactions of these bacteria with the host cells or their influence on them via bacterial soluble components may link local H. pylori infection in the gastric mucosa with the development of a systemic inflammatory response [ 5 , 6 ]. Previously, we showed that H. pylori infection acts synergistically with a high fat diet in the development of proinflammatory and proatherogenic endothelial cell environments in an experimental model of Caviae porcellus [ 7 ]. The arteries of H. pylori infected animals, regardless of diet, were less elastic, suggesting the role of the infectious agent in arterial stiffness.…”

“…We also showed the infiltration of inflammatory cells into the internal wall of the endothelium. Using an in vitro model of human THP-1 monocytes, we observed that H. pylori components, mainly proteins, induced strong foam-forming, comparable to 7-kCh, which was used as positive control [ 7 ].…”

Interference of LPS H. pylori with IL-33-Driven Regeneration of Caviae porcellus Primary Gastric Epithelial Cells and Fibroblasts

“…Hoyt et al, using the model of cultured pulmonary artery endothelial cells, showed that collagen is a survival factor against LPS-induced apoptosis [58]. Recently, Krupa et al showed the increased collagen I response of vascular endothelial cells exposed to LPS H. pylori [59]. In this study, in the milieu of LPS H. pylori and IL-33, migration of cells did not exceed 40% confluence, which may suggest some interference between bacterial LPS and host IL-33 signaling.…”