Obstructive Sleep Apnea-Induced Hypertension Is Associated With Increased Gut and Neuroinflammation
Journal of the American Heart Association(2023)
摘要
BackgroundObstructive sleep apnea (OSA) is an independent risk factor for the development of hypertension. We have demonstrated that OSA induces gut dysbiosis, and this dysbiotic microbiota contributes to hypertension. However, the mechanisms linking gut dysbiosis to blood pressure regulation remain unclear. Recent studies demonstrate that gut dysbiosis can induce a proinflammatory response of the host resulting in peripheral and neuroinflammation, key factors in the development of hypertension. We hypothesized that OSA induces inflammation in the gut that contributes to neuroinflammation and hypertension. Methods and ResultsOSA was induced in 8-week-old male rats. After 2 weeks of apneas, lymphocytes were isolated from aorta, brain, cecum, ileum, mesenteric lymph node, and spleen for flow cytometry. To examine the role of interleukin-17a, a monoclonal antibody was administered to neutralize interleukin-17a. Lymphocytes originating from the gut were tracked by labeling with carboxyfluorescein succinimidyl ester dye. OSA led to a significant decrease in T regulatory cells along with an increase in T helper (T-H) 17 cells in the ileum, cecum, and brain. Interleukin-17a neutralization significantly reduced blood pressure, increased T regulatory cells, and decreased T(H)1 cells in the ileum, cecum, and brain of OSA rats. T(H)1, T(H)2, and T(H)17 cells from the gut were found to migrate to the mesenteric lymph node, spleen, and brain with increased frequency in rats with OSA. ConclusionsOSA induces a proinflammatory response in the gut and brain that involves interleukin-17a signaling. Gut dysbiosis may serve as the trigger for gut and neuroinflammation, and treatments to prevent or reverse gut dysbiosis may prove useful in reducing neuroinflammation and hypertension.
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关键词
dysbiosis,gut microbiota,inflammation,microbiota-gut-brain axis,neuroinflammation
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