Zhang Jianwei, Yang Zicong, Liang Zhishan, Wang Mengjie, Hu Changxing, Chang Chao, Shi Lei, Ji Qingwei, Liu Ling
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, The Key Laboratory of Remodeling-related Cardiovascular Disease, Ministry of Education, Beijing, 100029, China.
Department of Cardiology, The People's Hospital of Guangxi Zhuang Autonomous Region, Nanning, China; Institute of Cardiovascular Sciences, Guangxi Academy of Medical Sciences, Nanning, China.
Eur J Pharmacol. 2022 May 15;923:174901. doi: 10.1016/j.ejphar.2022.174901. Epub 2022 Mar 30.
Atherosclerosis and its sequelae, such as coronary artery disease (CAD), are the most common diseases worldwide and the leading causes of morbidity and mortality in most countries. Our previous studies have shown that circulating secreted frizzled-related protein 4 (SFRP4) levels are increased in patients with CAD. However, the role of SFRP4 in the development of atherosclerosis remains unclear; thus, the purpose of this study was to determine the effect of SFRP4 on high-fat diet (HFD)-induced atherosclerosis and explore the possible mechanisms. In this study, we found for the first time that administration of recombinant SFRP4 alleviates atherosclerosis in ApoE-/- mice by reducing inflammation and oxidative stress. In addition, the anti-atherosclerotic effect of SFRP4 was associated with inhibition of the Wnt/β-catenin signaling pathway, and Wnt1 overexpression abolished the anti-atherosclerotic effects of SFRP4. Taken together, our results highlight the potential beneficial effect of SFRP4 as a therapeutic agent for atherosclerosis and CAD.
动脉粥样硬化及其后遗症，如冠状动脉疾病（CAD），是全球最常见的疾病，也是大多数国家发病和死亡的主要原因。我们之前的研究表明，CAD患者循环中分泌型卷曲相关蛋白4（SFRP4）水平升高。然而，SFRP4在动脉粥样硬化发展中的作用仍不清楚；因此，本研究的目的是确定SFRP4对高脂饮食（HFD）诱导的动脉粥样硬化的影响，并探索可能的机制。在本研究中，我们首次发现给予重组SFRP4可通过减轻炎症和氧化应激来减轻ApoE-/-小鼠的动脉粥样硬化。此外，SFRP4的抗动脉粥样硬化作用与抑制Wnt/β-连环蛋白信号通路有关，Wnt1过表达消除了SFRP4的抗动脉粥样硬化作用。综上所述，我们的结果突出了SFRP4作为动脉粥样硬化和CAD治疗剂的潜在有益作用。
