Key Laboratory of Targeted Intervention of Cardiovascular Disease, Collaborative Innovation Center of Translational Medicine for Cardiovascular Disease, Nanjing Medical University, Nanjing, Jiangsu 211166, China; Department of Physiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
Department of Pathophysiology, Nanjing Medical University, Nanjing, Jiangsu 211166, China.
J Nutr Biochem. 2019 Oct;72:108212. doi: 10.1016/j.jnutbio.2019.07.003. Epub 2019 Jul 8.
Migration of vascular smooth muscle cell (VSMC) plays a critical role in the pathophysiology of hypertension and several other vascular diseases. Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione), a bioactive constituent from Curcuma longa, is commonly used as a spice, food additive or dietary pigment. It has several health benefits including antioxidant, anti-inflammatory and anticancer properties. This study examined the roles of curcumin in VSMC migration in hypertension and underlying mechanism. VSMC was isolated and prepared from thoracic aorta of Wistar-Kyoto rats and spontaneously hypertensive rats (SHR). VSMC migration was evaluated with Boyden chamber assay and wound-healing assay. Curcumin attenuated VSMC migration, inhibited nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) expression and reduced interleukin (IL)-1β concentration in VSMC of SHR, which were similar to the effects of NLRP3 knockdown on IL-1β concentration and VSMC migration. Curcumin inhibited NFκB activation in VSMC of SHR, which was similar to the effects of NFκB inhibitor BAY11-7082 on NFκB activation. In another in vitro model of rat VSMC migration, curcumin also inhibited angiotensin II-induced VSMC migration, NFκB activation, NLRP3 expression and IL-1β production. Intragastric administration of curcumin in SHR attenuated hypertension and reduced NFκB activation, NLRP3 and matrix metalloproteinase-9 expressions and aortic media thickness. These results indicate that curcumin inhibits VSMC migration via inhibiting NFκB-mediated NLRP3 expression in VSMC of SHR or in angiotensin II-treated VSMC. Curcumin attenuates hypertension, vascular inflammation and vascular remodeling in SHR.
血管平滑肌细胞（VSMC）的迁移在高血压和几种其他血管疾病的病理生理学中起着关键作用。姜黄素（1,7-双（4-羟基-3-甲氧基苯基）-1,6-庚二烯-3,5-二酮）是姜黄中的一种生物活性成分，通常用作香料、食品添加剂或膳食色素。它具有多种健康益处，包括抗氧化、抗炎和抗癌特性。本研究探讨了姜黄素在高血压中 VSMC 迁移中的作用及其潜在机制。VSMC 是从 Wistar-Kyoto 大鼠和自发性高血压大鼠（SHR）的胸主动脉中分离和制备的。通过 Boyden 室测定和划痕愈合测定评估 VSMC 迁移。姜黄素可减轻 SHR 中 VSMC 的迁移，抑制核苷酸结合寡聚化结构域样受体蛋白 3（NLRP3）的表达，并降低 VSMC 中白细胞介素（IL）-1β的浓度，这与 NLRP3 敲低对 IL-1β浓度和 VSMC 迁移的影响相似。姜黄素抑制 SHR 中 VSMC 的 NFκB 激活，这与 NFκB 抑制剂 BAY11-7082 对 NFκB 激活的作用相似。在另一个大鼠 VSMC 迁移的体外模型中，姜黄素还抑制血管紧张素 II 诱导的 VSMC 迁移、NFκB 激活、NLRP3 表达和 IL-1β产生。姜黄素在 SHR 中的胃内给药可减轻高血压并降低 NFκB 激活、NLRP3 和基质金属蛋白酶-9 的表达以及主动脉中层厚度。这些结果表明，姜黄素通过抑制 NFκB 介导的 SHR 或血管紧张素 II 处理的 VSMC 中的 NLRP3 表达来抑制 VSMC 迁移。姜黄素可减轻 SHR 中的高血压、血管炎症和血管重塑。
