Dietary 7-ketocholesterol exacerbates myocardial ischemia-reperfusion injury in mice through monocyte/macrophage-mediated inflammation.

Autor: Uchikawa T; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.; Division of Cardiovascular Medicine, Faculty of Medical Sciences, Research Institute of Angiocardiology, Kyushu University, Fukuoka, Japan., Matoba T; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan. matoba@cardiol.med.kyushu-u.ac.jp., Kawahara T; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.; Division of Cardiovascular Medicine, Faculty of Medical Sciences, Research Institute of Angiocardiology, Kyushu University, Fukuoka, Japan., Baba I; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.; Division of Cardiovascular Medicine, Faculty of Medical Sciences, Research Institute of Angiocardiology, Kyushu University, Fukuoka, Japan., Katsuki S; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan., Koga JI; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan., Hashimoto Y; Department of Neurology, Graduate School of Medical Sciences, Neurological Institute, Kyushu University, Fukuoka, Japan., Yamasaki R; Department of Neurology, Graduate School of Medical Sciences, Neurological Institute, Kyushu University, Fukuoka, Japan., Ichi I; Graduate School of Humanities and Science, Ochanomizu University, Tokyo, Japan., Akita H; Laboratory of DDS Design and Drug Disposition, Graduate School of Pharmaceutical Sciences, Chiba University, Chiba, Japan., Tsutsui H; Department of Cardiovascular Medicine, Graduate School of Medical Sciences, Kyushu University, 3-1-1, Maidashi, Higashi-Ku, Fukuoka, 812-8582, Japan.; Division of Cardiovascular Medicine, Faculty of Medical Sciences, Research Institute of Angiocardiology, Kyushu University, Fukuoka, Japan.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2022 Sep 01; Vol. 12 (1), pp. 14902. Date of Electronic Publication: 2022 Sep 01.
DOI: 10.1038/s41598-022-19065-z
Abstrakt: Emerging evidence suggests that 7-ketocholesterol (7-KC), one of the most abundant dietary oxysterols, causes inflammation and cardiovascular diseases. Here we show the deteriorating effects of dietary 7-KC on myocardial ischemia-reperfusion (IR) injury and detailed the molecular mechanisms. A high-fat high-cholesterol diet containing 7-KC (7KWD) for 3 weeks increased the plasma 7-KC level compared with high-fat high-cholesterol diet in mice. In wild-type mice but not in CCR2 -/- mice, dietary 7-KC increased the myocardial infarct size after IR. Flow cytometry revealed that the ratio of Ly-6C high inflammatory monocytes to total monocytes was increased in the 7KWD group. Unbiased RNA sequencing using murine primary macrophages revealed that 7-KC regulated the expression of transcripts related to inflammation and cholesterol biosynthesis. We further validated that in vitro, 7-KC induced endoplasmic reticulum stress, mitochondrial reactive oxygen species production, and nuclear factor-kappa B activation, which are associated with increased mRNA levels of proinflammatory cytokines. Administration of N-acetyl-L-cysteine or siRNA-mediated knockdown of PKR-like endoplasmic reticulum kinase or endoplasmic reticulum oxidase 1α suppressed the levels of 7-KC-induced inflammation. Dietary 7-KC exacerbates myocardial IR injury through monocyte/macrophage-mediated inflammation. Endoplasmic reticulum stress and oxidative stress are involved in the 7-KC-induced proinflammatory response in macrophages.
(© 2022. The Author(s).)
Databáze: MEDLINE
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