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Antiinflammatory actions of inorganic nitrate stabilize the atherosclerotic plaque

2017; National Academy of Sciences; Volume: 114; Issue: 4 Linguagem: Inglês

10.1073/pnas.1613063114

1091-6490

Rayomand S. Khambata, Suborno M. Ghosh, Krishnaraj S. Rathod, Tharssana Thevathasan, Federica Filomena, Qingzhong Xiao, Amrita Ahluwalia,

Neuroinflammation and Neurodegeneration Mechanisms

Significance Reduced bioavailable nitric oxide generated within the vascular wall is a key pathogenic mechanism involved in the formation and rupture of an atheromatous plaque, the latter leading to myocardial infarction or stroke. We show that inorganic nitrate supplementation through delivery of nitric oxide reduces systemic leukocyte rolling and adherence, circulating neutrophil numbers, and monocyte activation through direct repression of neutrophil activation and up-regulation of interleukin-10–dependent antiinflammatory pathways in athero-prone mice. These antiinflammatory effects of inorganic nitrate result in reduced macrophage content of atherosclerotic plaques coupled with an elevation of smooth muscle content, resulting in a stable plaque phenotype. Our data suggest that inorganic nitrate supplementation has antiinflammatory effects, which may have clinical utility in the prophylaxis of atheroma development.