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Differential protein expression in hypertrophic heart with and without hypertension in spontaneously hypertensive
Xian Jin1, Li Xia, Li-Shun Wang
1Department of Geriatrics, Ren-Ji Hospital, Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education [corrected] Shanghai Jiao-Tong University Medical School, Shanghai, PR China.
Insights
Early metabolic changes, including increased glycolysis, occur in the hypertrophied heart before hypertension develops. Oxidative stress also plays a key role in cardiac hypertrophy.
Area of Science:
- Cardiovascular Biology
- Proteomics
- Molecular Mechanisms of Disease
Background:
- Cardiac hypertrophy is a known consequence of hypertension.
- The precise molecular mechanisms driving cardiac hypertrophy remain largely unknown.
- Understanding these mechanisms is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the protein expression profiles in the myocardium of spontaneously hypertensive rats (SHR) compared to Wistar-Kyoto (WKY) rats.
- To identify molecular changes associated with cardiac hypertrophy at different stages of hypertension development.
- To elucidate the role of energy metabolism and oxidative stress in hypertensive cardiac hypertrophy.
Main Methods:
- Two-dimensional gel electrophoresis (2-DE) combined with MALDI-TOF/TOF MS/MS was used to analyze protein expression.
- Comparative proteomic analysis was performed on left ventricular myocardial samples from SHR and WKY rats at various ages.
- Effects of renin-angiotensin-aldosterone system inhibitors (losartan, enalapril) were assessed on protein expression changes.
Main Results:
- Twenty proteins showed modulated expression in the hypertrophic myocardium of SHR.
- Thirteen proteins exhibited significant changes at an early stage, preceding sustained hypertension.
- Seven proteins changed at a later stage and were reversible with treatment, suggesting involvement of the renin-angiotensin-aldosterone system.
Conclusions:
- Early alterations in energy metabolism, favoring glycolysis over fatty acid and glucose oxidation, occur in SHR hearts before hypertension.
- Oxidative stress is implicated as a significant factor in the development of cardiac hypertrophy associated with hypertension.
- These findings provide insights into the early molecular events driving cardiac hypertrophy in hypertension.
Abstract:
Although cardiac hypertrophy in hypertension has been well recognized, the molecular mechanisms for the development of hypertrophy are still largely unknown. In this study, the protein expression profiles of left ventricular myocardia in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at different ages were analyzed using 2-DE in combination with MALDI-TOF/TOF MS/MS. The results showed that 20 proteins were modulated in the hypertrophic myocardium. Out of these modulated proteins, 13 proteins presented significant changes in SHR at an early stage prior to the development of sustained hypertension, while the changes of the other 7 protein expressions occurred only at a late stage in SHR when the blood pressure was significantly elevated, and were largely reversible by treatment with rennin-angiotensin-aldosterone system inhibitors losartan or enalapril. These data demonstrate that the changes in energy metabolism in the hypertrophied heart favor an increase in glycolysis and a decrease in oxidation of fatty acid and glucose, which occur at an early stage in SHR without hypertension. Our results also provide evidence to support the hypothesis that oxidative stress plays an important role in the development of hypertensive cardiac hypertrophy.
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