Gut lumen-leaked microbial DNA causes myocardial inflammation and impairs cardiac contractility in ageing mouse heart.
Gut lumen-leaked microbial DNA causes myocardial inflammation and impairs cardiac contractility in ageing mouse heart.
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DOI：
10.3389/fimmu.2023.1216344
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
--
作者：
新出现的证据表明，微生物群在衰老过程中介导宿主心脏功能中起着关键作用，然而，在衰老过程中微生物群与心脏细胞之间的通信机制尚未完全阐明。细菌DNA在老年人和小鼠的心肌细胞中富集。抗生素治疗显着降低了衰老小鼠的细菌DNA丰度。含有细胞外囊泡（mEV）的肠道微生物DNA很容易泄漏到血液中，并渗透到衰老小鼠的心肌细胞中，导致心脏微生物DNA富集。Vsig 4+巨噬细胞有效地阻断肠道mEV的扩散，而Vsig 4+细胞群在衰老小鼠中大大减少。肠道mEV治疗导致年轻Vsig 4-/-小鼠的心脏炎症和心脏收缩力降低。微生物DNA消耗减弱了肠道mEV的致病作用。cGAS/STING信号传导对于微生物DNA的作用至关重要。在老龄WT小鼠中恢复Vsig 4+巨噬细胞群体减少了心脏微生物DNA丰度和炎症，并改善了心脏收缩力。
Emerging evidence indicates the critical roles of microbiota in mediating host cardiac functions in ageing, however, the mechanisms underlying the communications between microbiota and cardiac cells during the ageing process have not been fully elucidated. Bacterial DNA was enriched in the cardiomyocytes of both ageing humans and mice. Antibiotic treatment remarkably reduced bacterial DNA abundance in ageing mice. Gut microbial DNA containing extracellular vesicles (mEVs) were readily leaked into the bloodstream and infiltrated into cardiomyocytes in ageing mice, causing cardiac microbial DNA enrichment. Vsig4+ macrophages efficiently block the spread of gut mEVs whereas Vsig4+ cell population was greatly decreased in ageing mice. Gut mEV treatment resulted in cardiac inflammation and a reduction in cardiac contractility in young Vsig4-/- mice. Microbial DNA depletion attenuated the pathogenic effects of gut mEVs. cGAS/STING signaling is critical for the effects of microbial DNA. Restoring Vsig4+ macrophage population in ageing WT mice reduced cardiac microbial DNA abundance and inflammation and improved heart contractility.
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影响因子：
29
作者：
Isaac R;Reis FCG;Ying W;Olefsky JM
通讯作者：
Olefsky JM
影响因子：
64.8
作者：
Konermann S;Brigham MD;Trevino AE;Joung J;Abudayyeh OO;Barcena C;Hsu PD;Habib N;Gootenberg JS;Nishimasu H;Nureki O;Zhang F
通讯作者：
Zhang F
影响因子：
3.7
作者：
Elderman M;Sovran B;Hugenholtz F;Graversen K;Huijskes M;Houtsma E;Belzer C;Boekschoten M;de Vos P;Dekker J;Wells J;Faas M
通讯作者：
Faas M
影响因子：
48
作者：
Callahan BJ;McMurdie PJ;Rosen MJ;Han AW;Johnson AJ;Holmes SP
通讯作者：
Holmes SP
DOI：
10.1038/s41569-018-0064-2
发表时间：
2018-09
期刊：
Nature reviews. Cardiology
影响因子：
--
作者：
Ferrucci L;Fabbri E
通讯作者：
Fabbri E