Editors' ChoiceAtherosclerosis

Bacteria-Driven Atherosclerosis

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Science Translational Medicine  14 May 2014:
Vol. 6, Issue 236, pp. 236ec83
DOI: 10.1126/scitranslmed.3009306

It has been hypothesized that bacterial infection could cause the formation of atherosclerotic lesions in arterial walls (known as atheromas). This “infection hypothesis” had fallen out of favor—until a new study by Khan et al. revisited this line of thought, reporting that Helicobacter cinaedi, a member of the Helicobacteraceae family, is a driver of atheroma development.

The authors demonstrated that oral infection with H. cinaedi promoted plaque formation in a hyperlipidemic, proatherogenic mouse model fed a high-cholesterol diet. When compared with uninfected controls, the lesions of the infected mice had more macrophages and neutrophils, and their aortas expressed higher amounts of proinflammatory genes. To gain insight into the mechanism by which H. cinaedi promotes lesion progression, Khan and colleagues infected peritoneal mouse macrophages and human monocyte-derived macrophages with the bacterium. Macrophages from both species showed elevated formation of foam cells (the lipid-laden macrophages that infiltrate fatty streaks and drive atheroma formation). The authors further demonstrated that mRNA for the H. cinaedi virulence factor, cytolethal distending toxin, was present in aortic lesions, suggesting its role in atherosclerosis pathogenesis.

Chronic inflammation is central to the initiation and progression of atherosclerotic plaques. In humans, H. cinaedi infection mostly manifests as cellulitis, meningitis, or enteritis in immunocompromised patients; however, the bacteria could also colonize the gastrointestinal tract of healthy persons and become a source of persistent infection. The hypothesis that pathogen-rooted chronic inflammation is causal in atherogenesis has been challenged by several failed antibiotic and vaccination clinical trials. The antibiotics may have missed the target on the specific pathogen or were not effective on plaques infested by multiple pathogens—possibilities that are substantiated by the new pathogen uncovered in the rodent and human lesions. The findings by Khan et al. necessitate further investigation of H. cinaedi and other enterohepatic Helicobacteraceae members’ contribution to inflammation and cardiovascular disease.

S. Khan et al., Promotion of atherosclerosis by Helicobacter cinaedi infection that involves macrophage-driven proinflammatory responses. Sci. Rep. 10.1038/srep04680 (2014). [Full Text]

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