ArticleCardiovascular diabetology2013
Protection of the heart by treatment with a divalent-copper-selective chelator reveals a novel mechanism underlying cardiomyopathy in diabetic rats.
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 34 papers.
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Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- Copper dysregulation in cardiometabolic disease: copper deficiency versus cuproptosis.Apoptosis : an international journal on programmed cell death · 2026Review
- From copper transport to cuproptosis: emerging therapeutic targets in cardiovascular disease.Molecular and cellular biochemistry · 2026Review
- Trientine ameliorates bleomycin-induced pulmonary fibrosis in rats through copper chelation and modulation of the CTR1/LOX/COL pathway.Inflammopharmacology · 2026Article
- Mechanisms and therapeutic strategies of copper homeostasis in the pathogenesis of sepsis-induced cardiomyopathy.Frontiers in cell and developmental biology · 2026Review
- Copper dyshomeostasis and cardiovascular disease: Molecular mechanisms and new strategies for targeted intervention with cuproptosis (Review).International journal of molecular medicine · 2026Review
- Novel impact of metal ion-induced cell death on diabetic cardiomyopathy pathogenesis and therapy.Apoptosis : an international journal on programmed cell death · 2025Review
- [Quercetin ameliorates myocardial injury in diabetic rats by regulating L-type calcium channels].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2025Article
- Copper ions: The invisible killer of cardiovascular disease (Review).Molecular medicine reports · 2024Review
- Diabetic Cardiomyopathy and Cell Death: Focus on Metal-Mediated Cell Death.Cardiovascular toxicology · 2024Review
- Role of copper and its complexes in cardiovascular diseases.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2023Article
- Rationale and design of a randomised trial of trientine in patients with hypertrophic cardiomyopathy.Heart (British Cardiac Society) · 2023Article
- CaBiomolecules · 2023Article
- Differential changes in cyclic adenosine 3'-5' monophosphate (cAMP) effectors and major CaJournal of cellular and molecular medicine · 2023Article
- Ferroptosis, necroptosis and cuproptosis: Novel forms of regulated cell death in diabetic cardiomyopathy.Frontiers in cardiovascular medicine · 2023Review
- Role of Trientine in Hypertrophic Cardiomyopathy: A Review of Mechanistic Aspects.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Review
- Copper chelation in patients with hypertrophic cardiomyopathy.Open heart · 2022Article
- The Molecular Mechanisms of Defective Copper Metabolism in Diabetic Cardiomyopathy.Oxidative medicine and cellular longevity · 2022Review
- Copper Preserves Vasculature Structure and Function by Protecting Endothelial Cells from Apoptosis in Ischemic Myocardium.Journal of cardiovascular translational research · 2021Article
- Calcium signaling in endocardial and epicardial ventricular myocytes from streptozotocin-induced diabetic rats.Journal of diabetes investigation · 2021Article
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIntracellular calcium (Ca²⁺) coordinates the cardiac contraction cycle and is dysregulated in diabetic cardiomyopathy. Treatment with triethylenetetramine (TETA), a divalent-copper-selective chelator, improves cardiac structure and function in patients and rats with diabetic cardiomyopathy, but the molecular basis of this action is uncertain. Here, we used TETA to probe potential linkages between left-ventricular (LV) copper and Ca²⁺ homeostasis, and cardiac function and structure in diabetic cardiomyopathy.
methodsWe treated streptozotocin-diabetic rats with a TETA-dosage known to ameliorate LV hypertrophy in patients with diabetic cardiomyopathy. Drug treatment was begun either one (preventative protocol) or eight (restorative protocol) weeks after diabetes induction and continued thereafter for seven or eight weeks, respectively. Total copper content of the LV wall was determined, and simultaneous measurements of intracellular calcium concentrations and isometric contraction were made in LV trabeculae isolated from control, diabetic and TETA-treated diabetic rats.
resultsTotal myocardial copper levels became deficient in untreated diabetes but were normalized by TETA-treatment. Cardiac contractility was markedly depressed by diabetes but TETA prevented this effect. Neither diabetes nor TETA exerted significant effects on peak or resting [Ca²⁺](i). However, diabetic rats showed extensive cardiac remodelling and decreased myofibrillar calcium sensitivity, consistent with observed increases in phosphorylation of troponin I, whereas these changes were all prevented by TETA.
conclusionsDiabetes causes cardiomyopathy through a copper-mediated mechanism that incorporates myocardial copper deficiency, whereas TETA treatment prevents this response and maintains the integrity of cardiac structure and myofibrillar calcium sensitivity. Altered calcium homeostasis may not be the primary defect in diabetic cardiomyopathy. Rather, a newly-described copper-mediated mechanism may cause this disease.
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