Institute of Life Science, Scuola Superiore Sant'Anna, Pisa, Italy.
Institute of Clinical Physiology of CNR, Via Giuseppe Moruzzi 1, 56124, Pisa, Italy.
Eur J Nutr. 2020 Oct;59(7):2953-2968. doi: 10.1007/s00394-019-02134-x. Epub 2019 Nov 9.
A regular intake of red grape juice has cardioprotective properties, but its role on the modulation of natriuretic peptides (NPs), in particular of C-type NP (CNP), has not yet been proven. The aims were to evaluate: (1) in vivo the effects of long-term intake of Tuscany Sangiovese grape juice (SGJ) on the NPs system in a mouse model of myocardial infarction (MI); (2) in vitro the response to SGJ small RNAs of murine MCEC-1 under physiological and ischemic condition; (3) the activation of CNP/NPR-B/NPR-C in healthy human subjects after 7 days' SGJ regular intake.
(1) C57BL/6J male and female mice (n = 33) were randomly subdivided into: SHAM (n = 7), MI (n = 15) and MI fed for 4 weeks with a normal chow supplemented with Tuscany SGJ (25% vol/vol, 200 µl/per day) (MI + SGJ, n = 11). Echocardiography and histological analyses were performed. Myocardial NPs transcriptional profile was investigated by Real-Time PCR. (2) MCEC-1 were treated for 24 h with a pool of SGJ small RNAs and cell viability under 24 h exposure to HO was evaluated by MTT assay. (3) Human blood samples were collected from seven subjects before and after the 7 days' intake of Tuscany SGJ. NPs and miRNA transcriptional profile were investigated by Real-Time PCR in MCEC-1 and human blood.
Our experimental data, obtained in a multimodal pipeline, suggest that the long-term intake of SGJ promotes an adaptive response of the myocardium to the ischemic microenvironment through the modulation of the cardiac CNP/NPR-B/NPR-C system.
Our results open new avenue in the development of functional foods aimed at enhancing cardioprotection of infarcted hearts through action on the myocardial epigenome.
经常摄入红葡萄汁具有心脏保护作用，但尚未证实其对利钠肽（NPs），特别是 C 型 NP（CNP）的调节作用。目的是评估：（1）在体内评估长期摄入托斯卡纳桑娇维塞葡萄汁（SGJ）对心肌梗死（MI）小鼠模型中 NPs 系统的影响；（2）在生理和缺血条件下，SGJ 小分子 RNA 对鼠 MCEC-1 的体外反应；（3）在健康人体中，连续 7 天饮用 SGJ 后，CNP/NPR-B/NPR-C 的激活。
（1）将 C57BL/6J 雄性和雌性小鼠（n=33）随机分为：SHAM（n=7）、MI（n=15）和 MI 喂食 4 周正常饲料，补充托斯卡纳 SGJ（25%vol/vol，200μl/天）（MI+SGJ，n=11）。进行超声心动图和组织学分析。通过实时 PCR 研究心肌 NPs 的转录谱。（2）MCEC-1 用 SGJ 小分子 RNA 混合物处理 24 小时，通过 MTT 测定评估 24 小时暴露于 HO 时细胞活力。（3）从 7 名受试者在饮用托斯卡纳 SGJ 7 天后采集血液样本。通过实时 PCR 在 MCEC-1 和人血中研究 NPs 和 miRNA 的转录谱。
我们的实验数据，通过多模式流水线获得，表明长期摄入 SGJ 通过调节心脏 CNP/NPR-B/NPR-C 系统，促进心肌对缺血微环境的适应反应。
我们的结果为开发功能性食品开辟了新途径，旨在通过作用于心肌表观基因组增强梗死心脏的心脏保护作用。
