血管平滑肌
血管紧张素II
化学
免疫印迹
刺激
炎症
肿瘤坏死因子α
内分泌学
内科学
医学
生物化学
平滑肌
受体
基因
作者
Ryohei Kuroda,Keisuke Okuno,Stephanie Cicalese,Yuriko Ueda,Yoshiharu Okuno,Ryohei Kono,Hirotoshi Utsunomiya,Shinsuke Marumoto,Satoru Eguchi
出处
期刊:Hypertension
[Ovid Technologies (Wolters Kluwer)]
日期:2021-09-01
卷期号:78 (Suppl_1)
标识
DOI:10.1161/hyp.78.suppl_1.p218
摘要
Ume ( Prunus mume ), is a traditional and familiar food in Asian countries, and is most often pickled or used to make wine and juice concentrate. Recently, Ume is attracting attention as a health food. We previously reported that Ume attenuates the activation of EGFR-ERK cascade and ROS production induced by angiotensin II (Ang II) in vascular smooth muscle cells (VSMC) of thoracic aorta. However, how Ume works on vascular inflammation and ER stress still remains unknown. AngII may enhance inflamm-aging via ER stress contributing to arterial stiffness and hypertension.We used primary culture of rat VSMC for experiment. We obtained 5 fractions (methanol, hexane, dichloromethane, ethyl acetate, and water) extracted from Ume juice. VSMC were pretreated with each fraction for 30 minutes followed by Ang II or tumor necrosis factor (TNF)-α stimulation. Stimulation period was 24 and 48 hours for Ang II, 6 hours for TNF-α. As the preliminary screening, we tested the cell response and solubility of each fraction (n=1~2). Pretreatment with 500μg/mL hexane fraction (PMF-H) showed the tendency to decrease VCAM1 expression under Ang II condition. PMF-H was completely soluble in the media at the concentration of 150 μg/mL. Based on this result, we focused on 150μg/mL PMF-H. DMSO was used as vehicle. In Western blot analysis, PMF-H attenuates ATF6 expression under both AII (p=0.0351, n=5) and TNF-α (p=0.0199, n=5) condition compared to vehicle. VCAM1 expression was significantly enhanced by Ang II stimulation (p=0.0471, n=5), and attenuated by PMF-H. PMF-H also reduced VCAM1 expression under TNF-α stimulation compared to vehicle (p=0.0377, n=5). GRP78 and Crystallin AB did not show any significant change. ATF6 and VCAM1 are key modulators of ER stress and vascular inflammation that may lead to cellular aging. Our results indicate PMF-H attenuates ATF6 and VCAM1 induced by Ang II or TNF-α stimulation. Thus, identification of the active ingredient in hexane fraction of Ume is desired as it may constitute a good candidate for a supplement or drug for anti-inflamm-aging therapy.
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