Influence of CagA-positive Helicobacter pylori strains on atherosclerotic carotid disease

Abstract

Citotoxin-associated gene-A (CagA)-positive Helicobacter pylori strains have been associated with occurrence and destabilization of coronary atherosclerotic plaques. However, data on the relationship between CagA-positive H. pylori infection and carotid artery instability are lacking. Thus, the role of CagA antigen in patients with symptomatic and asymptomatic carotid atherosclerotic plaques was investigated. A total of 64 patients with advanced carotid artery stenosis, including 33 patients with symptomatic and 31 patients with asymptomatic internal carotid artery stenosis, verified by duplex ultrasound, all undergoing carotid endarterectomy, were studied. The control group consisted of 65 subjects without a history or presence of vascular diseases. Serology for H. pylori and CagA antigen was assessed in all participants. Specimens of atherosclerotic plaques obtained from all patients during carotid endarterectomy were analyzed immunohistochemically using anti-CagA monoclonal antibodies. The ultrasonographic plaque characteristics were also estimated. CagA antibody titers were significantly higher in symptomatic patients (8.8; range, 5.8-32.7) compared to asymptomatic patients (4.7; range, 2.1-8.8; P = 0.005) and the control group (5.0; range 2.2-7.9; P < 0.001). There was significant difference in echolucency (≥ 25% soft material) between the symptomatic and asymptomatic groups (P = 0.034) by ultrasonographic evaluation. Positive immunoreactivity between monoclonal CagA antibodies and antigens within atherosclerotic specimens was significantly higher among symptomatic patients compared to asymptomatic patients (97.0 vs. 74.2%; P = 0.009). H. pylori may play a role in the pathogenesis of the atherosclerotic process due to autoimmune mechanisms and even contribute to destabilization of carotid atherosclerotic plaques.

Helicobacter pylori—An Infectious Risk Factor for Atherosclerosis?

“…For instance, anti-CagA antibodies are capable of reacting with both bacterial CagA and proteins present in the walls of medium-and large-sized arteries, providing evidence of molecular mimicry between CagA and vascular antigens 14) . Specifically, previous results have shown that anti-CagA antibodies exhibit immunohistochemical cross-reactions with antigens expressed by the cells involved in atherogenic processes, such as vascular smooth muscle cells, fibroblast-like cells in intimal atherosclerotic plaques and endothelial cells 118) . Taken together, these findings provide experimental evidence for the existence of molecular mimicry between CagA antigen and vascular wall peptides and lend biological plausibility to the theory that H. pylori infection plays a role in the pathogenesis of atherosclerosis.…”

Gastric Autoantigenic Proteins inHelicobacter PyloriInfection

“…The results suggest that an autoimmune reaction might be involved in the pathogenesis of not only H. pylori -associated gastrointestinal disorders, but also extra-intestinal autoimmune disorders. Autoantigens reported to be involved in diverse autoimmune disorders associated with H. pylori infection include carbonic anhydrase II similar alpha carbonic anhydrase of H. pylori in autoimmune pancreatitis,20 anti-CagA antibody, anti-HSP 65 antibody, and anti-HSP 60 antibody in artherosclerosis,21-23 anti-CagA antibody in Graves disease,24 anti-platelet glycoprotein antibody in immune thrombocytopenic purpura,25 proteins from endothelial or smooth muscle cells against CagA in hypertension,26 and HSP 60 of H. pylori associated with Sjogren syndrome 27. A healthy human body has immune regulatory systems including Treg cells.…”

Progress in cerebrovascular disease research in the last year

“…Specifically, citotoxin-associated gene A (CagA)-positive strains of HP have been found to be significantly more prevalent among patients with carotid artery atherosclerosis and ischemic stroke than in healthy subjects. The study by Rožanković et al [6] aimed to clarify whether an association exists between (CagA)-positive strains of HP and carotid plaque instability. A total of 64 patients with advanced carotid artery stenosis[70% (33 of them with symptomatic carotid disease) and treated with carotid endarterectomy were included in the study and compared with data from 65 subjects without vascular disease.…”