Abstract | BACKGROUND: METHODS: We 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. RESULTS: Total 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. CONCLUSIONS: Diabetes 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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Authors | Lin Zhang, Marie-Louise Ward, Anthony R J Phillips, Shaoping Zhang, John Kennedy, Bernard Barry, Mark B Cannell, Garth J S Cooper |
Journal | Cardiovascular diabetology
(Cardiovasc Diabetol)
Vol. 12
Pg. 123
(Aug 28 2013)
ISSN: 1475-2840 [Electronic] England |
PMID | 23981320
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Cardiotonic Agents
- Chelating Agents
- Troponin I
- Copper
- Trientine
- Calcium
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Topics |
- Animals
- Calcium
(metabolism)
- Cardiotonic Agents
(pharmacology)
- Chelating Agents
(pharmacology)
- Copper
(metabolism)
- Diabetes Mellitus, Experimental
(complications, drug therapy, metabolism, physiopathology)
- Diabetic Cardiomyopathies
(etiology, metabolism, physiopathology, prevention & control)
- Heart Rate
(drug effects)
- Hypertrophy, Left Ventricular
(etiology, metabolism, prevention & control)
- Isometric Contraction
(drug effects)
- Male
- Myocardial Contraction
(drug effects)
- Myocardium
(metabolism)
- Myofibrils
(drug effects, metabolism)
- Phosphorylation
- Rats
- Rats, Wistar
- Time Factors
- Trientine
(pharmacology)
- Troponin I
(metabolism)
- Ventricular Function, Left
(drug effects)
- Ventricular Remodeling
(drug effects)
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