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Left ventricular diastolic dysfunction in type 2 diabetes mellitus model rats.
Takehisa Abe1, Yoshimi Ohga, Nobuoki Tabayashi
1Department of Physiology II, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634-8521, Japan.
American Journal of Physiology. Heart and Circulatory Physiology
|December 19, 2001
Summary
Diabetic cardiomyopathy in type 2 diabetes mellitus (DM) is linked to impaired cardiac relaxation (lusitropy). Reduced expression of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) is the primary cause of this dysfunction.
Area of Science:
- Cardiovascular Physiology
- Metabolic Disease Research
- Molecular Cardiology
Background:
- Diabetic cardiomyopathy (DCM) is a significant complication of diabetes mellitus (DM).
- Understanding the underlying mechanisms of DCM is crucial for developing effective treatments.
- Otsuka Long-Evans Tokushima Fatty (OLETF) rats serve as a relevant model for type 2 DM.
Purpose of the Study:
- To investigate the relationship between left ventricular mechanical work and energetics in OLETF rats with type 2 DM.
- To identify the specific cardiac functional deficits contributing to diabetic cardiomyopathy.
Main Methods:
- Assessment of left ventricular systolic function, coronary flow, and coronary flow reserve in OLETF rats.
- Measurement of oxygen consumption related to mechanical work and contraction.
- Analysis of myosin isozyme transformation and maximum pacing rate.
- Evaluation of left ventricular relaxation rate and Ca(2+) handling in excitation-contraction coupling.
- Quantification of sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA2) protein levels.
Main Results:
- No significant differences in left ventricular systolic function, mean coronary flow, or coronary flow reserve were observed, even in late-stage DM rats.
- Myosin isozyme shifted from V(1) to V(3), and the maximum pacing rate decreased.
- Left ventricular relaxation rate was significantly slower in late DM rats (P < 0.05).
- Oxygen consumption per minute for Ca(2+) handling, primarily by SERCA2, was reduced without changes in basal metabolism or mitochondrial oxidative phosphorylation.
- SERCA2 protein levels were significantly lower in severe DM rats (P < 0.001).
Conclusions:
- Lusitropic dysfunction, specifically impaired cardiac relaxation, is the primary contributor to diabetic cardiomyopathy in this type 2 DM rat model.
- Depressed expression of SERCA2 is directly linked to the observed lusitropic dysfunction.
- These findings highlight SERCA2 as a key molecular target in the pathogenesis of diabetic cardiomyopathy.