Atorvastatin Attenuates Endothelial Cell Injury in Atherosclerosis Through Inhibiting ACSL4-Mediated Ferroptosis

IF 3.4 4区 医学 Q2 CARDIAC & CARDIOVASCULAR SYSTEMS Cardiovascular Therapeutics Pub Date : 2024-06-20 DOI:10.1155/2024/5522013
Huilian Tan, Ling Liu, Yanchao Qi, Dahong Zhang, Yanchun Zhi, Yu Li, Huimin Zhang, Jun Liu
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Abstract

Objective: This study is aimed at investigating the effects of atorvastatin (ATV) on endothelial cell injury in atherosclerosis (AS) through inhibiting acyl-CoA synthetase long-chain family member 4 (ACSL4)-mediated ferroptosis.

Methods: Human umbilical vein endothelial cells (HUVECs) were treated with oxidized low-density lipoprotein (ox-LDL) to establish an in vitro model of AS. The cell viability, lactate dehydrogenase (LDH) release, apoptosis, and expression levels of apoptotic proteins were assessed. The levels of inflammatory factors and adhesion molecules were determined by ELISA and Western blot, respectively. Cellular iron content, lipid peroxidation, glutathione (GSH) levels, and lipid reactive oxygen species (ROS) were measured. ACSL4 overexpression was performed to investigate its role in ATV-mediated protection against ferroptosis.

Results: ATV alleviated ox-LDL-induced HUVEC damage by restoring cell viability, reducing LDH levels, and inhibiting apoptosis. It also attenuated inflammation and adhesion by decreasing the levels of inflammatory factors TNF-α, IL-6, and IL-8, as well as adhesion molecules ICAM-1 and VCAM-1. ATV inhibited ferroptosis by regulating iron content, malondialdehyde (MDA) levels, ROS levels, and ACSL4 protein expression. Overexpression of ACSL4 (oe-ACSL4) hindered the protective effects of ATV on cell viability, antiapoptotic protein expression, LDH levels, apoptosis, and inflammatory factors.

Conclusion: Our findings suggest that ATV attenuates endothelial cell injury in AS by inhibiting ACSL4-mediated ferroptosis. These results provide insights into the potential therapeutic strategies for the treatment of AS.

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阿托伐他汀通过抑制 ACSL4 介导的铁蛋白沉积减轻动脉粥样硬化中的内皮细胞损伤
研究目的方法:用氧化低密度脂蛋白(ox-LDL)处理人脐静脉内皮细胞(HUVECs),建立动脉粥样硬化(AS)的体外模型。评估了细胞活力、乳酸脱氢酶(LDH)释放、细胞凋亡和凋亡蛋白的表达水平。炎症因子和粘附分子的水平分别通过 ELISA 和 Western 印迹法测定。还测定了细胞铁含量、脂质过氧化、谷胱甘肽(GSH)水平和脂质活性氧(ROS)。进行了 ACSL4 的过表达,以研究其在 ATV 介导的铁变态反应保护中的作用:结果:ATV 通过恢复细胞活力、降低 LDH 水平和抑制细胞凋亡减轻了氧化-LDL 诱导的 HUVEC 损伤。它还通过降低炎症因子 TNF-α、IL-6 和 IL-8 以及粘附分子 ICAM-1 和 VCAM-1 的水平来减轻炎症和粘附。ATV 通过调节铁含量、丙二醛(MDA)水平、ROS 水平和 ACSL4 蛋白表达来抑制铁变态反应。ACSL4(oe-ACSL4)的过表达阻碍了ATV对细胞活力、抗凋亡蛋白表达、LDH水平、细胞凋亡和炎症因子的保护作用:我们的研究结果表明,ATV 可通过抑制 ACSL4 介导的铁凋亡减轻强直性脊柱炎的内皮细胞损伤。这些结果为治疗强直性脊柱炎的潜在治疗策略提供了启示。
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来源期刊
Cardiovascular Therapeutics
Cardiovascular Therapeutics 医学-心血管系统
CiteScore
5.60
自引率
0.00%
发文量
55
审稿时长
6 months
期刊介绍: Cardiovascular Therapeutics (formerly Cardiovascular Drug Reviews) is a peer-reviewed, Open Access journal that publishes original research and review articles focusing on cardiovascular and clinical pharmacology, as well as clinical trials of new cardiovascular therapies. Articles on translational research, pharmacogenomics and personalized medicine, device, gene and cell therapies, and pharmacoepidemiology are also encouraged. Subject areas include (but are by no means limited to): Acute coronary syndrome Arrhythmias Atherosclerosis Basic cardiac electrophysiology Cardiac catheterization Cardiac remodeling Coagulation and thrombosis Diabetic cardiovascular disease Heart failure (systolic HF, HFrEF, diastolic HF, HFpEF) Hyperlipidemia Hypertension Ischemic heart disease Vascular biology Ventricular assist devices Molecular cardio-biology Myocardial regeneration Lipoprotein metabolism Radial artery access Percutaneous coronary intervention Transcatheter aortic and mitral valve replacement.
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