Sun Haijian, Zhu Xuexue, Zhou Yuetao, Cai Weiwei, Qiu Liying
Department of Basic Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi 214122, China.
Department of Basic Medicine, Wuxi Medical School, Jiangnan University, 1800 Lihu Avenue, Wuxi 214122, China.
Int J Mol Sci. 2017 May 26;18(6):1097. doi: 10.3390/ijms18061097.
Oxidized low-density lipoprotein (ox-LDL) accumulation is one of the critical determinants in endothelial dysfunction in many cardiovascular diseases such as atherosclerosis. C1q/TNF-related protein 9 (CTRP9) is identified to be an adipocytokine with cardioprotective properties. However, the potential roles of CTRP9 in endothelial function remain largely elusive. In the present study, the effects of CTRP9 on the proliferation, apoptosis, migration, angiogenesis, nitric oxide (NO) production and oxidative stress in human umbilical vein endothelial cells (HUVECs) exposed to ox-LDL were investigated. We observed that treatment with ox-LDL inhibited the proliferation, migration, angiogenesis and the generation of NO, while stimulated the apoptosis and reactive oxygen species (ROS) production in HUVECs. Incubation of HUVECs with CTRP9 rescued ox-LDL-induced endothelial injury. CTRP9 treatment reversed ox-LDL-evoked decreases in antioxidant enzymes including heme oxygenase-1 (HO-1), nicotinamide adenine dinucleotide phosphate (NAD(P)H) dehydrogenase quinone 1, and glutamate-cysteine ligase (GCL), as well as endothelial nitric oxide synthase (eNOS). Furthermore, CTRP9 induced activation of peroxisome proliferator-activated receptor γ co-activator 1α (PGC1-α) and phosphorylation of adenosine monophosphate-activated protein kinase (AMPK). Of interest, AMPK inhibition or PGC1-α silencing abolished CTRP9-mediated antioxidant enzymes levels, eNOS expressions, and endothelial protective effects. Collectively, we provided the first evidence that CTRP9 attenuated ox-LDL-induced endothelial injury by antioxidant enzyme inductions dependent on PGC-1α/AMPK activation.
氧化型低密度脂蛋白（ox-LDL）的蓄积是动脉粥样硬化等多种心血管疾病中内皮功能障碍的关键决定因素之一。C1q/TNF相关蛋白9（CTRP9）被确定为一种具有心脏保护特性的脂肪细胞因子。然而，CTRP9在内皮功能中的潜在作用仍 largely难以捉摸。在本研究中，研究了CTRP9对暴露于ox-LDL的人脐静脉内皮细胞（HUVECs）的增殖、凋亡、迁移、血管生成、一氧化氮（NO）生成和氧化应激的影响。我们观察到，用ox-LDL处理可抑制HUVECs的增殖、迁移、血管生成和NO生成，同时刺激其凋亡和活性氧（ROS）生成。用CTRP9孵育HUVECs可挽救ox-LDL诱导的内皮损伤。CTRP9处理可逆转ox-LDL引起的抗氧化酶水平下降，这些抗氧化酶包括血红素加氧酶-1（HO-1）、烟酰胺腺嘌呤二核苷酸磷酸（NAD(P)H）脱氢酶醌1和谷氨酸-半胱氨酸连接酶（GCL），以及内皮型一氧化氮合酶（eNOS）。此外，CTRP9诱导过氧化物酶体增殖物激活受体γ共激活因子1α（PGC1-α）的激活和腺苷单磷酸激活蛋白激酶（AMPK）的磷酸化。有趣的是，AMPK抑制或PGC1-α沉默消除了CTRP9介导的抗氧化酶水平、eNOS表达和内皮保护作用。总体而言，我们提供了首个证据，即CTRP9通过依赖PGC-1α/AMPK激活的抗氧化酶诱导作用减轻ox-LDL诱导的内皮损伤。
