ArticleInternational journal of molecular medicine2018
Inhibition of proprotein convertase subtilisin/kexin type 9 attenuates neuronal apoptosis following focal cerebral ischemia via apolipoprotein E receptor 2 downregulation in hyperlipidemic mice.
Article in International journal of molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07466251 (PCSK9 Inhibitor for Intracranial Atherosclerosis Related Acute Ischemic Stroke), which is not on this map. Cited by 24 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
PCSK9 Inhibitor for Intracranial Atherosclerosis Related Acute Ischemic Stroke (PISTIAS-3): a Randomized, Double-blind, Placebo-controlled Trial
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Lentivirus- or AAV-mediated gene therapy interventions in ischemic stroke: A systematic review of preclinicalJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2022Pooled it
- Clinical Outcomes of Early Administration of Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors in East Asian Patients with Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.Journal of clinical medicine · 2026Review
- Mechanisms of action and therapeutic potential of PCSK9-regulating drugs.Pharmaceutical biology · 2025Review
- Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9): The Multifaceted Biology, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9) to tackle central nervous system diseases: role as a promising approach.European journal of medical research · 2025Review
- The HNRNPC/CELF2 signaling pathway drives glycolytic reprogramming and mitochondrial dysfunction in drug-resistant acute myeloid leukemia.Cell & bioscience · 2025Article
- Sodium Alginate Hydrogel Infusion of Bone Marrow Mesenchymal Stem Cell-Derived Extracellular Vesicles and p38α Antagonistic Peptides in Myocardial Infarction Fibrosis Mitigation.Journal of the American Heart Association · 2025Article
- PCSK9 Manipulates Lipid Metabolism and the Immune Microenvironment in Cancer.OncoTargets and therapy · 2025Review
- The Emerging Role of PCSK9 in the Pathogenesis of Alzheimer's Disease: A Possible Target for the Disease Treatment.International journal of molecular sciences · 2024Review
- Inhibition of PCSK9 Protects against Cerebral Ischemia‒Reperfusion Injury via Attenuating Microcirculatory Dysfunction.Neurochemical research · 2024Article
- E3 ubiquitin ligase MARCH1 reduces inflammation and pyroptosis in cerebral ischemia-reperfusion injury via PCSK9 downregulation.Mammalian genome : official journal of the International Mammalian Genome Society · 2024Article
- Surfeit Locus Protein 4 as a Novel Target for Therapeutic Intervention in Cerebral Ischemia-Reperfusion Injury.Molecular neurobiology · 2024Article
- Targeting proprotein convertase subtilisin/kexin type 9 (PCSK9): from bench to bedside.Signal transduction and targeted therapy · 2024Review
- Case Report: Neurological adverse events in subject with myasthenia gravis after PCSK9 inhibitor administration.Frontiers in cardiovascular medicine · 2024Article
- LncRNA AGAP2 antisense RNA 1 stabilized by insulin-like growth factor 2 mRNA binding protein 3 promotes macrophage M2 polarization in clear cell renal cell carcinoma through regulation of the microRNA-9-5p/THBS2/PI3K-Akt pathway.Cancer cell international · 2023Article
- Metabolomics: A useful tool for ischemic stroke research.Journal of pharmaceutical analysis · 2023Review
- PCSK9 Affects Astrocyte Cholesterol Metabolism and Reduces Neuron Cholesterol Supplying In Vitro: Potential Implications in Alzheimer's Disease.International journal of molecular sciences · 2022Article
- The Emerging Roles of Intracellular PCSK9 and Their Implications in Endoplasmic Reticulum Stress and Metabolic Diseases.Metabolites · 2022Review
- Protective Mechanism of Proprotein Convertase Subtilisin-Like Kexin Type 9 Inhibitor on Rats with Middle Cerebral Artery Occlusion-Induced Cerebral Ischemic Infarction.Computational intelligence and neuroscience · 2022Article
- PCSK9 and the Gut-Liver-Brain Axis: A Novel Therapeutic Target for Immune Regulation in Alcohol Use Disorder.Journal of clinical medicine · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The inhibition of proprotein convertase subtilisin/kexin type 9 (PCSK9) protects a variety of cell types against neuronal apoptosis by binding to apolipoprotein E receptor 2 (ApoER2). The present study aimed to determine the association between PCSK9/ApoER2 signaling and neuronal apoptosis following middle cerebral artery occlusion (MCAO) injury in hyperlipidemic mice. For this purpose, C57BL/6 mice fed with a high‑fat diet (HFD) for 6 weeks were exposed to MCAO. Subsequently, PCSK9 was inhibited by a lentiviral vector harboring short‑hairpin RNA (shRNA) targeting PCSK9, which was stereotaxically injected into the cerebral cortex of mice. At 48 h post‑ischemia, hematoxylin‑eosin staining and a terminal deoxynucleotidyl transferase dUTP nick end labeling assay were performed to determine cerebral tissue injury and apoptosis. PCSK9 and ApoER2 expression levels were assessed by reverse transcription‑quantitative polymerase chain reaction, immunohistochemistry and western blotting. The results indicated that hyperlipidemia and increased PCSK9 expression were evident in HFD mice. Cerebral histological injury and neuronal apoptosis, as well as PCSK9 and ApoER2 levels, which were increased upon ischemia in hyperlipidemic mice, were attenuated by PCSK9 shRNA treatment. These protective effects of PCSK9 shRNA interference were associated with decreased neuronal apoptosis and a reduced level of ApoER2 expression in the hippocampus and cortex. The data of the present study demonstrated that the PCSK9 shRNA‑mediated anti‑apoptotic effect induced by MCAO in hyperlipidemic mice is associated with ApoER2 downregulation, which may be a potential new therapy for stroke treatment in patients with hyperlipidemia.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.