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Molecular basis of regression of cardiac hypertrophy
B Chevalier1, F Callens-el Amrani, C Heymes
1U127-INSERM, Hopital Lariboisière, Paris, France.
Abstract:
Cardiac hypertrophy due to a chronic mechanical overload puts into play a biologic cascade, including a trigger (the mechanical stretch), a transmitter (very likely to be the phosphoinositol pathway), and the final target (which is the DNA). The permanent changes in genetic expression resulting from the activation of this cascade allows the heart to produce normal active tension at a lower cost in terms of energy expenditure. The process is reversible, providing the treatment reduces the real load on the heart--i.e., not only the peripheral resistances but also the aortic impedance--during a period of time that has to be several times the half-life of cardiac proteins, and also that the treatment has an effect on the detrimental consequences of cardiac hypertrophy, namely, the systolic and diastolic dysfunction and the incidence of arrhythmias. In this report semisenescent spontaneously hypertensive rats were treated for 3 months with the converting enzyme inhibitor trandolapril. The treatment had a rather modest effect on blood pressure but resulted in a pronounced reduction in cardiac hypertrophy and in cardiac fibrosis, an improved coronary reserve, and attenuated both the effects of anoxia on the left ventricular diastolic compliance and the incidence of ventricular arrhythmias.
Insights
Trandolapril treatment reduced cardiac hypertrophy and fibrosis in hypertensive rats. This intervention improved cardiac function and decreased arrhythmias, demonstrating its therapeutic potential for heart conditions.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Chronic mechanical overload triggers a biologic cascade leading to cardiac hypertrophy.
- Cardiac hypertrophy involves genetic expression changes for energy-efficient tension production.
- This condition is reversible if cardiac load is reduced and detrimental effects are treated.
Purpose of the Study:
- To investigate the effects of trandolapril on cardiac hypertrophy and related cardiac dysfunctions.
- To assess the impact of a converting enzyme inhibitor on cardiac fibrosis, coronary reserve, and arrhythmias.
Main Methods:
- Semisenescent spontaneously hypertensive rats were treated with trandolapril for 3 months.
- Evaluated effects on blood pressure, cardiac hypertrophy, fibrosis, coronary reserve, and ventricular arrhythmias.
Main Results:
- Trandolapril showed a modest effect on blood pressure but significantly reduced cardiac hypertrophy and fibrosis.
- Improved coronary reserve and attenuated negative effects of anoxia on diastolic compliance were observed.
- The incidence of ventricular arrhythmias was also reduced.
Conclusions:
- Trandolapril effectively mitigates cardiac hypertrophy, fibrosis, and diastolic dysfunction in a model of hypertension.
- The drug improves cardiac function and reduces arrhythmia incidence, offering therapeutic benefits for pressure-overloaded hearts.