Dynamic changes of hemodynamic parameters and cardiac transcription of sirtuins in adaptive and mal-adaptive phases of pressure overload-induced hypertrophy in rats

Introduction: The aim of the study was to investigate the structural and hemodynamic changes as well as cardiac transcriptional profile of the key regulatory proteins, sirtuins family (SIRT1-7), in adaptive and mal-adaptive phases of left ventricular hypertrophy (LVH). Methods: LVH was induced in male Wistar rats (190±20g) by abdominal aortic banding. The third and sixteenth weeks post-surgery were considered as adaptive and mal-adaptive phases of hypertrophy (H3w and H16w groups, respectively). Blood pressure (BP) was recorded through the carotid artery catheter. Cell area and fibrosis were assessed using haematoxylin/eosin and Masson trichrome staining, respectively. The sirtuins mRNA levels were quantified using quantitative RT–PCR technique. Results: H3w rats had a higher systolic and diastolic BP, cardiomyocytes area and heart to body weight ratio (HW/BW) compared with control (intact animals). Although cell size and HW/BW increased in the H16w group, systolic and diastolic BP did not change significantly in comparison with control. In H3w group, SIRT1/3/6/7 mRNAs levels increased significantly. In H16w group, SIRT1/3/5/6/7 mRNAs levels declined in comparison with H3w group. SIRT2 and SIRT4 mRNA levels did not change significantly among the experimental groups. Conclusion: During progression of cardiac hypertrophy transcriptional profile of sirtuins changes in parallel to structural and hemodynamic parameters. Therefore, it can validate sirtuins as the pharmacological targets for the treatment of pathological LVH.