Tsai Kun-Ling, Kao Chung-Lan, Hung Ching-Hsia, Cheng Yung-Hsin, Lin Huei-Chen, Chu Pei-Ming
Department of Physical Therapy, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Department of Physical Medicine and Rehabilitation, Taipei Veterans General Hospital, Taipei, Taiwan.
Oncotarget. 2017 May 2;8(18):29600-29612. doi: 10.18632/oncotarget.16768.
Atherosclerotic cardiovascular disease is linked to both oxidative stress and endothelial cell dysfunction. Chicoric acid has antioxidant and anti-inflammatory properties. In the present investigation, we demonstrated that chicoric acid inhibits oxidized low-density lipoprotein (oxLDL)-facilitated dysfunction in human umbilical vein endothelial cells (HUVECs). Oxidative injuries were tested by investigating the formation of intracellular reactive oxygen species (ROS) and by examining the activity of antioxidant enzymes and the function of endothelial nitric oxide synthase (eNOS). We also confirmed that chicoric acid mitigates apoptotic features caused by oxLDL, such as the subsequent break down of mitochondrial transmembrane potential and the activation of Bax, which promote DNA strand breaks and activate caspase-3. Moreover, our data revealed that chicoric acid attenuated the oxLDL activation of NF-κB, the attachment of THP-1 cells and the overexpression of adhesion molecules in human endothelial cells. The results of this study suggest a potential molecular mechanism through which chicoric acid inhibits oxLDL-induced human endothelial dysfunction.
动脉粥样硬化性心血管疾病与氧化应激和内皮细胞功能障碍均有关联。菊苣酸具有抗氧化和抗炎特性。在本研究中,我们证明菊苣酸可抑制人脐静脉内皮细胞(HUVECs)中氧化型低密度脂蛋白(oxLDL)诱导的功能障碍。通过检测细胞内活性氧(ROS)的形成、抗氧化酶的活性以及内皮型一氧化氮合酶(eNOS)的功能来评估氧化损伤。我们还证实菊苣酸可减轻oxLDL引起的凋亡特征,如随后的线粒体跨膜电位破坏和促凋亡蛋白Bax的激活,Bax会促进DNA链断裂并激活半胱天冬酶-3。此外,我们的数据显示菊苣酸可减弱oxLDL对核因子κB(NF-κB)的激活、THP-1细胞的黏附以及人内皮细胞中黏附分子的过表达。本研究结果提示了菊苣酸抑制oxLDL诱导的人内皮功能障碍的潜在分子机制。