Chen Youming, Wang Lan, Huang Shixing, Ke Jiangfeng, Wang Qing, Zhou Zhiwen, Chang Wei
Department of Cardiology, Shanghai Jiaotong University Affiliated Sixth People's Hospital, Shanghai, China.
Department of Radiology, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Redox Biol. 2021 Aug;44:102020. doi: 10.1016/j.redox.2021.102020. Epub 2021 May 25.
Oxidative stress plays a critical role in the development of cardiac remodeling and heart failure. Lutein, the predominant nonvitamin A carotenoid, has been shown to have profound effects on oxidative stress. However, the effect of lutein on angiotensin II (Ang II)-induced cardiac remodeling and heart failure remains unknown.
The aim of this study was to determine whether lutein is involved in cardiac remodeling and to elucidate the underlying molecular mechanisms.
In vitro experiments with isolated neonatal rat cardiomyocytes (NRCMs) and cardiac fibroblasts (CFs) revealed that lutein significantly attenuated Ang II-induced collagen expression in CFs, and cardiomyocyte hypertrophy. The Ang II-induced increases in superoxide generation, inflammation and apoptosis in cultured CFs were strikingly prevented by lutein. In vivo, fibrosis, hypertrophic cardiomyocyte and superoxide generation were analyzed, and lutein was demonstrated to confer resistance to Ang II-induced cardiac remodeling in mice. Mechanistically, RNA sequencing revealed that interleukin-11 (IL-11) expression was significantly upregulated in mouse hearts in response to Ang II infusion and was significantly suppressed in the hearts of lutein-treated mice. Furthermore, IL-11 overexpression blocked the effects of lutein on fibrosis and oxidative stress in CFs and impaired the protective effect of lutein on cardiac remodeling. Notably, we discovered that lutein could reduce Ang II-induced IL-11 expression, at least partly through the regulation of activator protein (AP)-1 expression and activity.
Lutein has potential as a treatment for cardiac remodeling and heart failure via the suppression of IL-11 expression.
氧化应激在心脏重塑和心力衰竭的发展过程中起着关键作用。叶黄素是主要的非维生素A类胡萝卜素，已被证明对氧化应激有深远影响。然而，叶黄素对血管紧张素II（Ang II）诱导的心脏重塑和心力衰竭的影响尚不清楚。
本研究旨在确定叶黄素是否参与心脏重塑，并阐明其潜在的分子机制。
对分离的新生大鼠心肌细胞（NRCMs）和心脏成纤维细胞（CFs）进行的体外实验表明，叶黄素可显著减弱Ang II诱导的CFs中胶原蛋白的表达以及心肌细胞肥大。叶黄素还能显著抑制Ang II诱导的培养CFs中超氧化物生成增加、炎症反应和细胞凋亡。在体内，分析了纤维化、肥大心肌细胞和超氧化物生成情况，结果表明叶黄素可使小鼠对Ang II诱导的心脏重塑产生抗性。从机制上来说，RNA测序显示，在Ang II灌注后，小鼠心脏中白细胞介素11（IL-11）的表达显著上调，而在叶黄素处理的小鼠心脏中则显著受到抑制。此外，IL-11过表达阻断了叶黄素对CFs纤维化和氧化应激的影响，并损害了叶黄素对心脏重塑的保护作用。值得注意的是，我们发现叶黄素可以至少部分地通过调节激活蛋白（AP）-1的表达和活性来降低Ang II诱导的IL-11表达。
叶黄素通过抑制IL-11表达，具有治疗心脏重塑和心力衰竭的潜力。
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