ArticleJournal of translational medicine2010
Prevention of hyperglycemia-induced myocardial apoptosis by gene silencing of Toll-like receptor-4.
Article in Journal of translational medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 1 of them a synthesis that pooled it.
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Who cites it
41 citing papers in PubMed, 1 synthesis or guideline pooled it, 69 citations in OpenAlex.
- Inhibition of Toll-like Receptor-4 expression for amelioration of myocardial injury in diabetes: A meta-analysis.Clinics (Sao Paulo, Brazil) · 2022Pooled it
- Inflammatory signalling in diabetic cardiomyopathy: molecular mechanisms and potential therapeutic strategies.Nature reviews. Cardiology · 2026Review
- Design, synthesis, biological evaluation, and in silico characterization of chalcone derivatives as antidiabetic hits.Scientific reports · 2026Article
- Loganic acid ameliorates diabetic cardiomyopathy via suppressing TLR4/p38 MAPK signaling-mediated oxidative stress and inflammation.Journal of clinical biochemistry and nutrition · 2025Article
- MOTS-c Peptide Attenuated Diabetic Cardiomyopathy in STZ-Induced Type 1 Diabetic Mouse Model.Cardiovascular drugs and therapy · 2025Article
- Therapeutic strategies targeting mechanisms of macrophages in diabetic heart disease.Cardiovascular diabetology · 2024Review
- Myricetin alleviates diabetic cardiomyopathy by regulating gut microbiota and their metabolites.Nutrition & diabetes · 2024Article
- Algae Food Products as a Healthcare Solution.Marine drugs · 2023Review
- Mitochondrial Impairment: A Link for Inflammatory Responses Activation in the Cardiorenal Syndrome Type 4.International journal of molecular sciences · 2023Review
- Article
- Costunolide alleviates hyperglycaemia-induced diabetic cardiomyopathy via inhibiting inflammatory responses and oxidative stress.Journal of cellular and molecular medicine · 2023Article
- Article
- Proinflammatory Cytokines Trigger the Onset of Retinal Abnormalities and Metabolic Dysregulation in a Hyperglycemic Mouse Model.Journal of ophthalmology · 2023Article
- Doxorubicin-induced apoptosis enhances monocyte infiltration and adverse cardiac remodeling in diabetic animals.Canadian journal of physiology and pharmacology · 2022Article
- The role of protein kinase C in diabetic microvascular complications.Frontiers in endocrinology · 2022Review
- Signaling Pathways Related to Oxidative Stress in Diabetic Cardiomyopathy.Frontiers in endocrinology · 2022Review
- Cancer and diabetes: the interlinking metabolic pathways and repurposing actions of antidiabetic drugs.Cancer cell international · 2021Review
- Diabetes-induced cardiomyopathy is ameliorated by heat-killed Lactobacillus reuteri GMNL-263 in diabetic rats via the repression of the toll-like receptor 4 pathway.European journal of nutrition · 2021Article
- The Akt pathway mediates the protective effects of myeloid differentiation protein 1 in pathological cardiac remodelling.ESC heart failure · 2021Article
- Roles of PRR-Mediated Signaling Pathways in the Regulation of Oxidative Stress and Inflammatory Diseases.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundApoptosis is an early event involved in cardiomyopathy associated with diabetes mellitus. Toll-like receptor (TLR) signaling triggers cell apoptosis through multiple mechanisms. Up-regulation of TLR4 expression has been shown in diabetic mice. This study aimed to delineate the role of TLR4 in myocardial apoptosis, and to block this process through gene silencing of TLR4 in the myocardia of diabetic mice.
methodsDiabetes was induced in C57/BL6 mice by the injection of streptozotocin. Diabetic mice were treated with 50 μg of TLR4 siRNA or scrambled siRNA as control. Myocardial apoptosis was determined by TUNEL assay.
resultsAfter 7 days of hyperglycemia, the level of TLR4 mRNA in myocardial tissue was significantly elevated. Treatment of TLR4 siRNA knocked down gene expression as well as diminished its elevation in diabetic mice. Apoptosis was evident in cardiac tissues of diabetic mice as detected by a TUNEL assay. In contrast, treatment with TLR4 siRNA minimized apoptosis in myocardial tissues. Mechanistically, caspase-3 activation was significantly inhibited in mice that were treated with TLR4 siRNA, but not in mice treated with control siRNA. Additionally, gene silencing of TLR4 resulted in suppression of apoptotic cascades, such as Fas and caspase-3 gene expression. TLR4 deficiency resulted in inhibition of reactive oxygen species (ROS) production and NADPH oxidase activity, suggesting suppression of hyperglycemia-induced apoptosis by TLR4 is associated with attenuation of oxidative stress to the cardiomyocytes.
conclusionsIn summary, we present novel evidence that TLR4 plays a critical role in cardiac apoptosis. This is the first demonstration of the prevention of cardiac apoptosis in diabetic mice through silencing of the TLR4 gene.
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