Current opinion in lipidology · 2025
The intestine and cardiovascular disease.
СтатьяОбзорПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Delk Samuel C, Reddy Srinivasa T, Fogelman Alan M
Аннотация
PURPOSE OF REVIEW: A review of recent publications demonstrating the important role of the intestine in the pathogenesis of cardiovascular disease.
RECENT FINDINGS: At baseline (≥ 6 months since myocardial infarction), the pattern of fecal microbiota and blood LPS levels after a meal predicted risk for new major adverse cardiovascular events over the next 7 years. In intestine, tryptophan is metabolized primarily by the kynurenine pathway, which is regulated by the enzyme indoleamine-2,3-dioxygenase 1 (IDO1). Tryptophan flow into the kynurenine pathway limits its availability for the formation of microbiota-derived indole derivatives including butyrate, and limits availability of tryptophan for the 5-hydroxytryptamine (5-HT or serotonin) pathway. Feeding Ldlr-/- mice a high-fat high-cholesterol diet (HFD+HCD) increased intestinal IDO1 activity, decreased levels of tryptophan, fecal butyrate, and 5-HT. Ldlr-/- mice deficient in intestinal Ido1 ( Ldlr-/-Ido1-/- ) on HFD+HCD had increased intestinal levels of 5-HT, increased gut permeability, increased gut inflammation, increased LPS, and increased aortic atherosclerosis. Ldlr-/- mice fed HFD+HCD and treated with a 5-HT pathway inhibitor had increased fecal indole levels, improved gut-barrier, increased antimicrobial peptide levels, and decreased aortic atherosclerosis without a change in plasma cholesterol.
SUMMARY: These studies demonstrate the importance of microbiota-derived products and intestinal tryptophan metabolism in atherosclerosis.
RECENT FINDINGS: At baseline (≥ 6 months since myocardial infarction), the pattern of fecal microbiota and blood LPS levels after a meal predicted risk for new major adverse cardiovascular events over the next 7 years. In intestine, tryptophan is metabolized primarily by the kynurenine pathway, which is regulated by the enzyme indoleamine-2,3-dioxygenase 1 (IDO1). Tryptophan flow into the kynurenine pathway limits its availability for the formation of microbiota-derived indole derivatives including butyrate, and limits availability of tryptophan for the 5-hydroxytryptamine (5-HT or serotonin) pathway. Feeding Ldlr-/- mice a high-fat high-cholesterol diet (HFD+HCD) increased intestinal IDO1 activity, decreased levels of tryptophan, fecal butyrate, and 5-HT. Ldlr-/- mice deficient in intestinal Ido1 ( Ldlr-/-Ido1-/- ) on HFD+HCD had increased intestinal levels of 5-HT, increased gut permeability, increased gut inflammation, increased LPS, and increased aortic atherosclerosis. Ldlr-/- mice fed HFD+HCD and treated with a 5-HT pathway inhibitor had increased fecal indole levels, improved gut-barrier, increased antimicrobial peptide levels, and decreased aortic atherosclerosis without a change in plasma cholesterol.
SUMMARY: These studies demonstrate the importance of microbiota-derived products and intestinal tryptophan metabolism in atherosclerosis.