Memantine, NMDA Receptor Antagonist, Attenuates ox-LDL-Induced Inflammation and Oxidative Stress via Activation of BDNF/
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ORIGINAL ARTICLE
Memantine, NMDA Receptor Antagonist, Attenuates ox-LDL-Induced Inflammation and Oxidative Stress via Activation of BDNF/TrkB Signaling Pathway in HUVECs Ying Hao ,1,4 Rui Xiong,2,4 and Xue Gong3 Received 28 July 2020; accepted 12 October 2020
Abstract— Atherosclerosis is a chronic cardiovascular disease and contributes to pathogenesis of
most myocardial infarction and ischemic stroke. Additionally, N-methyl-D-aspartate (NMDA) receptor plays a crucial role in myocardial infarction and ischemic strokes. The aim of our study was to investigate the underlying mechanisms of memantine (MEM), the blocker of NMDA receptors, in the development of atherosclerosis. In our study, human umbilical vascular endothelial cells (HUVECs) were stimulated with low-density lipoprotein (ox-LDL) to establish an atherosclerotic cell model. Cell Counting Kit-8 (CCK-8) assay and TUNEL staining were performed to detect the cell activity and apoptosis of HUVECs, respectively. The levels of inflammatory cytokines and malondialdehyde and the activities of lactate dehydrogenase (LDH), superoxide dismutase (SOD), and caspase-1 were quantified with commercial assay kits. Finally, qRT-PCR assay and western blot analysis were carried out to determine the mRNA and protein expressions of inflammation-related genes in HUVECs. The results of the present study suggested that ox-LDL stimulation induced decreased viability of HUVECs, excessive inflammation, and oxidative stress, while these effects were counteracted by MEM treatment. Interestingly, MEM triggered the activation of BDNF/TrkB signaling pathway in HUVECs, and K252a, the inhibitor of the BDNF/TrkB pathway, abolished the suppressive effect of MEM on ox-LDLinduced inflammation, oxidative stress, and apoptosis in HUVECs. Overall, MEM attenuated oxLDL-induced inflammation, oxidative stress, and apoptosis via activation of BDNF/TrkB signaling pathway in HUVECs, indicating that MEM may be defined as a novel and effective agent for atherosclerosis treatment. KEY WORDS: atherosclerosis; N-methyl-D-aspartate (NMDA) receptor; memantine; inflammation; oxidative stress.
Ying Hao and Rui Xiong contributed equally to this work. 1
Department of Cardiology, Shanghai East Hospital, Tongji University, 1800 Yuntai Rd, Shanghai, 200126, People’s Republic of China 2 Department of Cornea, Affiliated Eye Hospital of Nanchang University, 463 Bayi Avenue, Nanchang City, 330006, Jiangxi Province, People’s Republic of China
3
Department of Cardiology, DeltaHealth Hospital, Shanghai, 201702, People’s Republic of China 4 To whom correspondence should be addressed to Ying Hao at Department of Cardiology, Shanghai East Hospital, Tongji University, 1800 Yuntai Rd, Shanghai, 200126, People’s Republic of China. E-mail: [email protected]; and ; [email protected]
0360-3997/20/0000-0001/0 # 2020 Springer Science+Business Media, LLC, part of Springer Nature
Hao, Xiong, and Gong INTRODUCTION Atherosclerosis is a low-grade and age-related cardiovascular disease characterized by chronic inflammation of the arter
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