Proteomic analysis of left ventricular diastolic dysfunction hearts in renovascular hypertensive rats.
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.
The Institute of Cardiovascular Disease, Division of Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, PR China.
Wang
W
Junhong
Yang
Y
Jing
Ma
M
Jizheng
Zhu
Z
Shushu
Chen
C
Xiangjian
Wu
W
Hengfang
Yang
Y
Di
Zhang
Z
Jinan
D000818:Animals; D015153:Blotting, Western; D019703:Calcineurin / Q000378:metabolism; D004452:Echocardiography; D054144:Heart Failure, Diastolic / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*; D006978:Hypertension, Renovascular / Q000150:complications; D008297:Male; D013058:Mass Spectrometry; D020543:Proteome / Q000032:analysis*; D040901:Proteomics / Q000379:methods*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D018487:Ventricular Dysfunction, Left / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology*
D020543:Proteome; D019703:Calcineurin