ArticleCardiovascular diabetology2013
Treatment with a copper-selective chelator causes substantive improvement in cardiac function of diabetic rats with left-ventricular impairment.
Article in Cardiovascular diabetology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 44 citations in OpenAlex.
- Copper dysregulation in cardiometabolic disease: copper deficiency versus cuproptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Copper dysregulation in cardiometabolic disease: copper deficiency versus cuproptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- Trientine ameliorates bleomycin-induced pulmonary fibrosis in rats through copper chelation and modulation of the CTR1/LOX/COL pathway.Inflammopharmacology · 2026Article
- The Yin and Yang of copper in cardiovascular health and disease.Molecular and cellular biochemistry · 2026Review
- Carbon Dot Integrated Cellulose-Based Green-Fluorescent Aerogel for Detection and Removal of Copper Ions in Water.Gels (Basel, Switzerland) · 2025Article
- Diabetic Cardiomyopathy and Cell Death: Focus on Metal-Mediated Cell Death.Cardiovascular toxicology · 2024Review
- Contaminant Metals and Cardiovascular Health.Journal of cardiovascular development and disease · 2023Review
- Searching for Effective Treatments in HFpEF: Implications for Modeling the Disease in Rodents.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy.Heart (British Cardiac Society) · 2023Article
- Copper homeostasis and copper-induced cell death in the pathogenesis of cardiovascular disease and therapeutic strategies.Cell death & disease · 2023Review
- ATF3/SPI1/SLC31A1 Signaling Promotes Cuproptosis Induced by Advanced Glycosylation End Products in Diabetic Myocardial Injury.International journal of molecular sciences · 2023Article
- Role of Trientine in Hypertrophic Cardiomyopathy: A Review of Mechanistic Aspects.Pharmaceuticals (Basel, Switzerland) · 2022Review
- The Molecular Mechanisms of Defective Copper Metabolism in Diabetic Cardiomyopathy.Oxidative medicine and cellular longevity · 2022Review
- Guan Xin Dan Shen formulation protectsMolecular medicine reports · 2021Article
- Article
- Antifibrotic and Regenerative Effects of Treamid in Pulmonary Fibrosis.International journal of molecular sciences · 2020Article
- Copper promotion of myocardial regeneration.Experimental biology and medicine (Maywood, N.J.) · 2020Review
- Bisamide Derivative of Dicarboxylic Acid Contributes to Restoration of Testicular Tissue Function and Influences Spermatogonial Stem Cells in Metabolic Disorders.Frontiers in cell and developmental biology · 2020Article
- The metabolic syndrome in heart failure: insights to specific mechanisms.Heart failure reviews · 2020Review
- Trientine selectively delivers copper to the heart and suppresses pressure overload-induced cardiac hypertrophy in rats.Experimental biology and medicine (Maywood, N.J.) · 2018Article
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDefective copper regulation is implicated as a causative mechanism of organ damage in diabetes. Treatment with trientine, a divalent-copper-selective chelator, improves arterial and renal structure/function in diabetes, wherein it also ameliorates left-ventricular (LV) hypertrophy. However, direct in vivo evidence that trientine can improve cardiac function in heart failure has hitherto been lacking.
methodsTo determine whether trientine treatment could improve in vivo outcome, we measured cardiac function in groups of trientine-treated diabetic (TETA-DIA), non-drug-treated diabetic (DIA) and sham-treated control (SHAM) rats, by using in vivo high-field cardiac magnetic-resonance imaging (cMRI) and an ex vivo isolated-perfused working heart method. Forty age-matched animals underwent a cMRI scan after which 12 were randomized to the SHAM group and 28 underwent streptozotocin-injection; of these, 25 developed stable diabetes, and 12 were then randomized to receive no treatment for 16 weeks (DIA) and the other 13 to undergo 8-weeks' untreated diabetes followed by 8-weeks' drug treatment (TETA-DIA). Animals were studied again by cMRI at 8 and 16 weeks following disease induction, and finally by measurement of ex vivo cardiac function.
resultsAfter eight weeks diabetes, rats (DIA/TETA-DIA) had developed significant impairment of LV function, as judged by impairment of ejection fraction (LVEF), cardiac output (CO), and LV mass (LVM)/body-mass (all P < 0.001), as well as other functional indexes. LVEF, CO (both P < 0.001) and the other indexes deteriorated further at 16 weeks in DIA, whereas trientine (TETA-DIA) improved cardiac function by elevating LVEF and CO (both P < 0.001), and also partially reversed the increase in LVM/body-mass (P < 0.05). In ex vivo hearts from DIA, the CO response to increasing preload pressure was deficient compared with SHAM (P < 0.001) whereas the preload-CO relationship was significantly improved in TETA-DIA animals (P < 0.001).
conclusionsTrientine treatment significantly improved cardiac function in diabetic rats with substantive LV impairment. These results implicate impaired copper regulation in the pathogenesis of impaired cardiac function caused by diabetic cardiomyopathy, and support ongoing studies of trientine treatment in patients with heart failure.
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