Panthiya Luckika, Tocharus Jiraporn, Chaichompoo Waraluck, Suksamrarn Apichart, Tocharus Chainarong
Department of Anatomy, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand.
Graduate School, Chiang Mai University, Chiang Mai 50200, Thailand.
EXCLI J. 2023 Jun 5;22:466-481. doi: 10.17179/excli2023-6124. eCollection 2023.
The proliferation and migration of vascular smooth muscle cells (VSMCs) play vital roles in the pathogenesis of atherosclerosis and hypertension. It has been proposed and verified that hexahydrocurcumin (HHC), a metabolite form of curcumin, has cardiovascular protective effects. This study examined the effect of HHC on angiotensin II (Ang II)-induced proliferation, migration, and inflammation in rat aortic VSMCs and explored the molecular mechanisms related to the processes. The results showed that HHC significantly suppressed Ang II-induced proliferation, migration, and inflammation in VSMCs. HHC inhibited Ang II-induction of the increase in cyclin D1 and decrease in p21 expression in VSMCs. Moreover, HHC attenuated the generation of reactive oxygen species (ROS), and the expression of nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and matrix metalloproteinases-9 (MMP9) in Ang II-induced VSMCs. The proliferation, migration, inflammation, and ROS production were also inhibited by GKT137831 (NADPH oxidase, NOX1/4 inhibitor) and the combination of HHC and GKT137831. In addition, HHC restored the Ang-II inhibited expression of peroxisome proliferator-activated receptor-γ (PPAR-γ) and peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). These findings indicate that HHC may play a protective role in Ang II-promoted proliferation, migration, and inflammation by suppressing NADPH oxidase mediated ROS generation and elevating PPAR-γ and PGC-1α expression. See also Figure 1(Fig. 1).
血管平滑肌细胞（VSMCs）的增殖和迁移在动脉粥样硬化和高血压的发病机制中起着至关重要的作用。姜黄素的代谢产物六氢姜黄素（HHC）已被提出并证实具有心血管保护作用。本研究检测了HHC对血管紧张素II（Ang II）诱导的大鼠主动脉VSMCs增殖、迁移和炎症的影响，并探讨了与之相关的分子机制。结果表明，HHC显著抑制了Ang II诱导的VSMCs增殖、迁移和炎症。HHC抑制了Ang II诱导的VSMCs中细胞周期蛋白D1增加和p21表达降低。此外，HHC减弱了Ang II诱导的VSMCs中活性氧（ROS）的生成以及核因子κB（NF-κB）、肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和基质金属蛋白酶-9（MMP9）的表达。GKT137831（NADPH氧化酶，NOX1/4抑制剂）以及HHC与GKT137831的联合使用也抑制了增殖、迁移、炎症和ROS生成。此外，HHC恢复了Ang-II抑制的过氧化物酶体增殖物激活受体-γ（PPAR-γ）和过氧化物酶体增殖物激活受体-γ共激活因子-1α（PGC-1α）的表达。这些发现表明，HHC可能通过抑制NADPH氧化酶介导的ROS生成并提高PPAR-γ和PGC-1α的表达，在Ang II促进的增殖、迁移和炎症中发挥保护作用。另见图1（图1）。
