Huilian Tan, Ling Liu, Yanchao Qi, Dahong Zhang, Yanchun Zhi, Yu Li, Huimin Zhang, Jun Liu
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引用次数: 0
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.
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.