Memantine, NMDA Receptor Antagonist, Attenuates ox-LDL-Induced Inflammation and Oxidative Stress via Activation of BDNF/TrkB Signaling Pathway in HUVECs.
Apoptosis
/ drug effects
Atherosclerosis
/ drug therapy
Biomarkers
/ metabolism
Blotting, Western
Brain-Derived Neurotrophic Factor
/ metabolism
Cells, Cultured
Cytokines
/ metabolism
Enzyme-Linked Immunosorbent Assay
Excitatory Amino Acid Antagonists
/ pharmacology
Human Umbilical Vein Endothelial Cells
/ drug effects
Humans
In Situ Nick-End Labeling
Inflammation
/ drug therapy
Lipoproteins, LDL
Memantine
/ pharmacology
Membrane Glycoproteins
/ metabolism
Oxidative Stress
/ drug effects
Receptor, trkB
/ metabolism
Receptors, N-Methyl-D-Aspartate
/ antagonists & inhibitors
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction
/ drug effects
N-methyl-D-aspartate (NMDA) receptor
atherosclerosis
inflammation
memantine
oxidative stress
Journal
Inflammation
ISSN: 1573-2576
Titre abrégé: Inflammation
Pays: United States
ID NLM: 7600105
Informations de publication
Date de publication:
Apr 2021
Apr 2021
Historique:
received:
28
07
2020
accepted:
12
10
2020
revised:
21
09
2020
pubmed:
12
11
2020
medline:
10
11
2021
entrez:
11
11
2020
Statut:
ppublish
Résumé
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-LDL-induced inflammation, oxidative stress, and apoptosis in HUVECs. Overall, MEM attenuated ox-LDL-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.
Identifiants
pubmed: 33174139
doi: 10.1007/s10753-020-01365-z
pii: 10.1007/s10753-020-01365-z
doi:
Substances chimiques
Biomarkers
0
Brain-Derived Neurotrophic Factor
0
Cytokines
0
Excitatory Amino Acid Antagonists
0
Lipoproteins, LDL
0
Membrane Glycoproteins
0
Receptors, N-Methyl-D-Aspartate
0
oxidized low density lipoprotein
0
BDNF protein, human
7171WSG8A2
Receptor, trkB
EC 2.7.10.1
tropomyosin-related kinase-B, human
EC 2.7.10.1
Memantine
W8O17SJF3T
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
659-670Subventions
Organisme : Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai
ID : No. PWZxq2017-05
Organisme : the Top-level Clinical Discipline Project of Shanghai Pudong
ID : No. PWYgf2018-02
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