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Proteomic analysis of left ventricular diastolic dysfunction hearts in renovascular hypertensive rats
Wang Junhong1, Yang Jing, Ma Jizheng
1The Institute of Cardiovascular Disease, Division of Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Insights
This study reveals key protein changes in hearts with renovascular hypertension-induced diastolic dysfunction. Decreased Calsarcin-1 (CS-1) protein is linked to calcineurin activity, offering insights into cardiac failure mechanisms.
Area of Science:
- Cardiovascular Proteomics
- Cardiac Physiology
- Molecular Cardiology
Background:
- Diastolic dysfunction is a common feature of cardiac failure, but its underlying molecular mechanisms remain unclear.
- Systemic hypertension is a major risk factor for developing diastolic dysfunction and subsequent heart failure.
- Understanding the proteomic alterations in diastolic dysfunction is crucial for identifying novel therapeutic targets.
Purpose of the Study:
- To investigate the proteomic changes in the left ventricle associated with renovascular hypertension-induced diastolic dysfunction.
- To identify specific proteins and molecular pathways involved in the development of diastolic dysfunction.
- To explore the relationship between Calsarcin-1 (CS-1) and calcineurin activity in this cardiac dysfunction model.
Main Methods:
- Differential proteomic profiling using 2D-electrophoresis and mass spectroscopy on rat hearts.
- Induction of renovascular hypertension using the two-kidneys, one-clip (2K1C) model in Sprague-Dawley rats.
- 2D echocardiography to assess left ventricular diastolic function and comparison with sham-operated controls.
Main Results:
- Sixteen altered protein spots were identified in the hearts of 2K1C rats with diastolic dysfunction.
- Calsarcin-1 (CS-1) was significantly down-regulated in 2K1C rats.
- A negative correlation was observed between CS-1 levels and calcineurin enzymatic activity (r(2)=0.72, p=0.03), alongside changes in cellular energy metabolism and thin filament proteome.
Conclusions:
- This study provides novel insights into the left ventricular proteome associated with systemic hypertension-induced diastolic dysfunction.
- The observed decrease in CS-1 protein and increased calcineurin activity suggest a significant role for CS-1 in calcineurin-mediated left ventricular hypertrophy.
- These findings highlight potential molecular targets for managing diastolic dysfunction in hypertensive heart disease.
Abstract:
Abnormalities of diastolic function are common to virtually all forms of cardiac failure. However, the molecular events leading to diastolic dysfunction have not been fully elucidated. We performed a differential proteomic profiling study on diastolic dysfunction hearts induced by renovascular hypertension. Left ventricular diastolic dysfunction induced by renovascular hypertension (2K1C, two-kidneys, one clip) was performed in twelve Sprague-Dawley rats. 2D echocardiographic and cardiac protein patterns (2D-electrophoresis and mass spectroscopy) were compared with the sham operated rats. We described sixteen altered protein spots in 2K1C rats with left ventricular diastolic dysfunction. Calsarcin-1 (CS-1) was significantly down-regulated in 2K1C rats and it showed a negative correlation with calcineurin enzymatic activity (r(2)=0.72 p=0.03). We also showed changes in cellular energy metabolism in 2K1C rats, and these changes go in parallel with alterations of the thin filament proteome responsible for actin-myosin cross-bridge. In conclusion, this study provides a new insight into the left ventricular proteome profile associated with systemic hypertension induced diastolic dysfunction in a renovascular hypertension rat model. The decreased CS-1 protein with a concomitant increased enzymatic activity of calcineurin, suggests an important role of CS-1 in the calcineurin-mediated left ventricular hypertrophy.
