Helicobacter Pylori Virulence Factor Cytotoxin-Associated Gene A (CagA) Induces Vascular Calcification in Coronary Artery Smooth Muscle Cells

Abstract

Helicobacter pylori (H. pylori) has been associated with cardiovascular diseases. The pro-inflammatory H. pylori virulence factor cytotoxin-associated gene A (CagA) has been detected in serum exosomes of H. pylori-infected subjects and may exert systemic effects throughout the cardiovascular system. The role of H. pylori and CagA in vascular calcification was hitherto unknown. The aim of this study was to determine the vascular effects of CagA through human coronary artery smooth muscle cell (CASMC) osteogenic and pro-inflammatory effector gene expression as well as interleukin 1β secretion and cellular calcification. CagA upregulated bone morphogenic protein 2 (BMP-2) associated with an osteogenic CASMC phenotype switch and induced increased cellular calcification. Furthermore, a pro-inflammatory response was observed. These results support that H. pylori may contribute to vascular calcification through CagA rendering CASMCs osteogenic and inducing calcification.

Can Pyomelanin Produced by Pseudomonas aeruginosa Promote the Regeneration of Gastric Epithelial Cells and Enhance Helicobacter pylori Phagocytosis?

“…VacA inhibits the lysosomal and autophagic killing of H. pylori , establishing an intracellular niche for bacterial survival in macrophages [ 11 ]. CagA is an oncoprotein that mediates a range of intra-cellular effects in gastric epithelial cells by affecting several signalling pathways to promote chronic inflammation and proliferation of gastric epithelial cells that change their polarity and morphology, contributing to an increased risk of gastritis or neoplasia [ 12 , 13 ].…”