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Research Article Open Access
Background: The mortality and morbidity of heart failure with preserved ejection fraction has increased. Sarcoplasmic reticulum Ca2+-ATPase type 2a (SERCA2a) regulates cardiac functions, and a reduction in SERCA2a expression has been documented in left ventricular (LV) diastolic dysfunction. By contrast, SERCA2a overexpression improves LV diastolic dysfunction. Thus, transcriptional regulation of SERCA2a may be a new therapeutic target. The aim of this study was to determine whether renal denervation, a treatment for resistant hypertension, is a regulator of SERCA2a transcription in vivo.
Methods: Uninephrectomy and 6-week salt loading in three-week-old male Sprague-Dawley rats were used to devise a cardiac diastolic dysfunction model, and mechanical renal denervation was performed. The expression of SERCA2a and related molecules was evaluated with quantitative polymerase chain reaction and western blot analyses. The maximal positive LV pressure development (+dP/dtmax) and time constant at the isovolumic relaxation phase (Tau) were determined with cardiac catheters.
Results: Uninephrectomy combined with a high-salt diet significantly reduced the messenger RNA expression and protein abundance of SERCA2a, which were restored by renal denervation. In accordance with changes in SERCA2a transcription, uninephrectomy and the high-salt diet decreased LV diastolic function, which was evaluated by Tau and restored by renal denervation. LV systolic function, measured with +dp/dtmax, was preserved. Renal denervation did not lower blood pressure, urinary protein levels, cardiac hypertrophy, or fibrosis.
Conclusions: We found that renal denervation is a regulator of SERCA2a transcription in vivo. Our data may provide new therapeutic insights into LV diastolic dysfunction and warrant further study.
Heart failure, Heart failure with preserved ejection fraction, Renal denervation, SERCA2a, Hypertension, Blood Pressure