ArticleJournal of molecular medicine (Berlin, Germany)2015
Inhibition of TLR4 attenuates vascular dysfunction and oxidative stress in diabetic rats.
Article in Journal of molecular medicine (Berlin, Germany), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 56 citations in OpenAlex.
- Cellular and Molecular Mechanisms of Hyperglycemia-Induced Atherosclerosis and Intervention Strategies of Chinese Herbal Medicine.Drug design, development and therapy · 2026Review
- Review
- Repurposing Antidiabetic Drugs for Gangrene: A Mendelian Randomization and Text Mining Study.International journal of medical sciences · 2025Article
- Effect of Tricin on cardiomyocyte damage caused by diabetic cardiomyopathy (DCM).BMC cardiovascular disorders · 2024Article
- Western diet promotes the progression of metabolic dysfunction-associated steatotic liver disease in association with ferroptosis in male mice.Physiological reports · 2024Article
- Hypoglycemic Ability of Sericin-Derived Oligopeptides (SDOs) fromFoods (Basel, Switzerland) · 2024Article
- Ischemic stroke and diabetes: a TLR4-mediated neuroinflammatory perspective.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Signaling pathways in vascular function and hypertension: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Obesity-related vascular dysfunction persists after weight loss and is associated with decreased vascular glucagon-like peptide receptor in female rats.American journal of physiology. Heart and circulatory physiology · 2022Article
- Vascular hyperacetylation is associated with vascular smooth muscle dysfunction in a rat model of non-obese type 2 diabetes.Molecular medicine (Cambridge, Mass.) · 2022Article
- Crosstalk of TLR4, vascular NADPH oxidase, and COVID-19 in diabetes: What are the potential implications?Vascular pharmacology · 2021Review
- Substance-P Inhibits Cardiac Microvascular Endothelial Dysfunction Caused by High Glucose-Induced Oxidative Stress.Antioxidants (Basel, Switzerland) · 2021Article
- Toll-Like Receptors in the Pathogenesis of Essential Hypertension. A Forthcoming Immune-Driven Theory in Full Effect.International journal of molecular sciences · 2021Review
- Novel Insights Into the Pathogenesis of Diabetic Cardiomyopathy and Pharmacological Strategies.Frontiers in cardiovascular medicine · 2021Review
- Sex Differences in the Vasodilation Mediated by G Protein-Coupled Estrogen Receptor (GPER) in Hypertensive Rats.Frontiers in physiology · 2021Article
- Anti-inflammatory activities of puerarin in high-fat diet-fed rats with streptozotocin-induced gestational diabetes mellitus.Molecular biology reports · 2020Article
- Blockade of the TLR4-MD2 complex lowers blood pressure and improves vascular function in a murine model of type 1 diabetes.Scientific reports · 2020Article
- Investigation of toll-like receptor (TLR) 4 inhibitor TAK-242 as a new potential anti-rheumatoid arthritis drug.Arthritis research & therapy · 2020Article
- Selenium-Containing Protein From Selenium-EnrichedFrontiers in physiology · 2020Article
- Article
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Authors and funding
5 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
unlabelledHyperglycemia-induced reactive oxygen species (ROS) production plays a major role in the pathogenesis of diabetic vascular dysfunction. However, the underlying mechanisms remain unclear. Toll-like receptor 4 (TLR4), a key component of innate immunity, is known to be activated during diabetes. Therefore, we hypothesize that hyperglycemia activates TLR4 signaling in vascular smooth muscle cells (VSMCs) that triggers ROS production and causes vascular dysfunction. Rat mesenteric VSMCs exposed to high glucose (25 mmol/l) increased TLR4 expression and activated TLR4 signaling via upregulation of myeloid differentiation factor 88 (MyD88). TLR4 inhibitor CLI-095 significantly attenuated elevated levels of ROS and nuclear factor-kappa B (NF-κB) activity in VSMCs exposed to high glucose. Mesenteric arteries from streptozotocin-induced diabetic rats treated with CLI-095 (2 mg/kg/day) intraperitoneally for 2 weeks exhibited reduced ROS generation and attenuated noradrenaline-induced contraction. These results suggest that hyperglycemia-induced ROS generation and NF-κB activation in VSMCs are at least, in part, mediated by TLR4 signaling. Therefore, strategies to block TLR4 signaling pathways pose a promising avenue to alleviate diabetic-induced vascular complications. KEY MESSAGES: High glucose-induced TLR4 activation in vascular smooth muscle cells. Inhibition of TLR4 attenuated high glucose-induced ROS production and NF-κB activity in VSMC. Suppression of TLR4 signaling attenuated mesenteric contraction in diabetic rat.
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