Phytomedicine : international journal of phytotherapy and phytopharmacology · 2026
Anacardic acid mitigates post‑MI cardiac fibrosis via suppressing p38/JNK-GATA3 pathway and H3K9ac‑dependent epigenetic regulation.
СтатьяНазвание 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.
Huang Wenjing, Wang Xuemei, Yan Xin, Wang Si, Lin Lan, Li Lingyu, Liu Linling, Wang Yingling, Li Xinyue, Mao Yan, Liu Xiao, Chen YiXin, Kong Jiayi, Shen Lin, Jiang Qiying, Li Ruli, Li He, Zhang Junyan, Zhang Ran, Wang Fan, Sun Xinyi, Guo Yingqiang, Jiang Wei
Аннотация
BACKGROUND: Myocardial fibrosis (MF), a hallmark of cardiovascular diseases (CVDs) such as myocardial infarction (MI), drives progressive cardiac dysfunction and adverse remodeling. Histone acetylation is a critical epigenetic regulator in cardiovascular pathology. Anacardic acid (AA), a histone acetyltransferase inhibitor (HATi) with pleiotropic bioactivities, has been studied in various disease contexts; however, its antifibrotic efficacy and mechanisms in MF remain unclear.
METHODS: In vivo, a mouse model of post-infarction MF was established by permanent left anterior descending (LAD) ligation. Using pirfenidone (PFD, an antifibrotic by inhibiting TGF-β) as a positive control, AA's effects were assessed by cardiac function, histopathology, and quantification of fibrotic burden. In vitro, primary cardiac fibroblasts (CFs) stimulated with TGF-β1 were used to delineate mechanisms, focusing on proliferation, migration, myofibroblast differentiation, and transcription of fibrosis-related genes.
RESULTS: In vivo, AA and PFD comparably attenuated cardiac fibrosis and collagen deposition, downregulated fibrosis-related gene expression, and improved heart failure biomarkers in MI mice. Transcriptomic profiling indicated that MAPK pathway and GATA3 expression were reduced in AA-treated MI mouse hearts but increased in CFs in human MI single-cell RNA-sequencing datasets. In vitro, AA inhibited TGF-β1-induced CF proliferation, migration, and myofibroblast differentiation by suppressing p38/JNK phosphorylation, limiting GATA3 nuclear translocation, and reducing H3K9ac levels, thereby decreasing transcription of α-SMA, Col1a1, and Col3a1.
CONCLUSIONS: AA protects against post-infarction MF by suppressing the p38/JNK-GATA3 pathway and downregulating H3K9ac-dependent epigenetic activation, supporting AA as a potential antifibrotic strategy and therapeutic candidate for cardiac fibrosis.
METHODS: In vivo, a mouse model of post-infarction MF was established by permanent left anterior descending (LAD) ligation. Using pirfenidone (PFD, an antifibrotic by inhibiting TGF-β) as a positive control, AA's effects were assessed by cardiac function, histopathology, and quantification of fibrotic burden. In vitro, primary cardiac fibroblasts (CFs) stimulated with TGF-β1 were used to delineate mechanisms, focusing on proliferation, migration, myofibroblast differentiation, and transcription of fibrosis-related genes.
RESULTS: In vivo, AA and PFD comparably attenuated cardiac fibrosis and collagen deposition, downregulated fibrosis-related gene expression, and improved heart failure biomarkers in MI mice. Transcriptomic profiling indicated that MAPK pathway and GATA3 expression were reduced in AA-treated MI mouse hearts but increased in CFs in human MI single-cell RNA-sequencing datasets. In vitro, AA inhibited TGF-β1-induced CF proliferation, migration, and myofibroblast differentiation by suppressing p38/JNK phosphorylation, limiting GATA3 nuclear translocation, and reducing H3K9ac levels, thereby decreasing transcription of α-SMA, Col1a1, and Col3a1.
CONCLUSIONS: AA protects against post-infarction MF by suppressing the p38/JNK-GATA3 pathway and downregulating H3K9ac-dependent epigenetic activation, supporting AA as a potential antifibrotic strategy and therapeutic candidate for cardiac fibrosis.