ArticleJournal of translational medicine2022
Alpha-ketoglutarate ameliorates abdominal aortic aneurysm via inhibiting PXDN/HOCL/ERK signaling pathways.
Article in Journal of translational medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 23 citations in OpenAlex.
- Nicotinamide adenine dinucleotide phosphate hydrogen oxidase 2 exacerbates abdominal aortic aneurysm formation by inducing oxidative stress through autophagy inhibition.Histology and histopathology · 2026Article
- OGDH mediates α-ketoglutarate-induced follicular development and antioxidative response by interacting with CAT/SOD2.Biological research · 2026Article
- Metabolic reprogramming in aortic diseases: insights from metabolomics and therapeutic opportunities.Medical review (2021) · 2026Review
- VSMCs and the immune microenvironment: a multidimensional regulatory network driving vascular injury and repair.Frontiers in immunology · 2026Review
- Macrophage-biomimetic nanomedicine for targeted therapy of abdominal aortic aneurysm via Nrf2/NF-κB pathway.Theranostics · 2026Article
- Macrophage Trem2 deficiency aggravates aging-induced vascular remodeling by acting as a non-classical receptor of interleukin-13.Molecular biomedicine · 2025Article
- Baicalin affects the progression of diabetic retinopathy through the RAGE/PXDN/PI3K/AKT pathway.Journal of translational medicine · 2025Article
- Vascular Smooth Muscle Cell Metabolic Disorders in the Occurrence and Development of Aortic Aneurysms and Dissections: Implications for Therapy.Biomedicines · 2025Review
- Alpha-ketoglutarate protects against myocardial infarction via FTO-mediated anti-inflammatory macrophage activation.Basic research in cardiology · 2025Article
- Cardioprotective and Anti-Hypertensive Effects of Epigallocatechin Gallate: Novel Insights Into Biological Evidence.Journal of clinical hypertension (Greenwich, Conn.) · 2025Review
- Sympathetic hyperinnervation drives abdominal aortic aneurysm development by promoting vascular smooth muscle cell phenotypic switching.Journal of advanced research · 2025Article
- Effects of α-Ketoglutarate Peripartum Supplementation on Reproductive, Lactational, Productive and Immunological Outcomes in Dairy Cows.Animals : an open access journal from MDPI · 2025Article
- Metabolomics, Genetics, and Environmental Factors: Intersecting Paths in Abdominal Aortic Aneurysm.International journal of molecular sciences · 2025Article
- Vinpocetine alleviates the abdominal aortic aneurysm progression via VSMCs SIRT1-p21 signaling pathway.Acta pharmacologica Sinica · 2025Article
- Oxidative stress in vascular surgical diseases: mechanisms, impacts and therapeutic perspectives.Frontiers in pharmacology · 2025Review
- Mechanisms of metabolic reprogramming in abdominal aortic aneurysm.Frontiers in cell and developmental biology · 2025Review
- Therapeutic Targeting of Signaling Pathways in Abdominal Aortic Aneurysm: From Pathogenesis to Precision Medicine.Drug design, development and therapy · 2025Review
- Exosomal miR-9-5p derived from iPSC-MSCs ameliorates doxorubicin-induced cardiomyopathy by inhibiting cardiomyocyte senescence.Journal of nanobiotechnology · 2024Article
- The role of oxidative stress in aortic dissection: a potential therapeutic target.Frontiers in cardiovascular medicine · 2024Review
- Targeting metabolism in aortic aneurysm and dissection: from basic research to clinical applications.International journal of biological sciences · 2023Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Abdominal aortic aneurysm (AAA) represents the serious vascular degenerative disorder, which causes high incidence and mortality. Alpha-ketoglutarate (AKG), a crucial metabolite in the tricarboxylic acid (TCA) cycle, has been reported to exert significant actions on the oxidative stress and inflammation. However, its role in AAA still remains elusive. Herein, we examined the effects of AKG on the formation of AAA. The study established an elastase-induced mouse abdominal aortic aneurysms model as well as a TNF-α-mediated vascular smooth muscle cells (VSMCs) model, respectively. We displayed that AKG pre-treatment remarkably prevented aneurysmal dilation assessed by diameter and volume and reduced aortic rupture. In addition, it was also observed that AKG treatment suppressed the development of AAA by attenuating the macrophage infiltration, elastin degradation and collagen fibers remodeling. In vitro, AKG potently decreased TNF-α-induced inflammatory cytokines overproduction, more apoptotic cells and excessive superoxide. Mechanistically, we discovered that upregulation of vpo1 in AAA was significantly suppressed by AKG treatment. By exploring the RNA-seq data, we found that AKG ameliorates AAA mostly though inhibiting oxidative stress and the inflammatory response. PXDN overexpression neutralized the inhibitory effects of AKG on ROS generation and inflammatory reaction in MOVAS. Furthermore, AKG treatment suppressed the expression of p-ERK1/2, 3-Cl Tyr in vivo and in vitro. ERK activator disrupted the protective of AKG on TNF-α-induced VSMCs phenotypic switch. Conclusively, AKG can serve as a beneficial therapy for AAA through regulating PXDN/HOCL/ERK signaling pathways.
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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.