Sirtuin 1 mediates the pro-survival effects of vitamin D in angiotensin II-induced hypertrophy of H9c2 cardiomyoblasts

BackgroundThe role of 1,25-dihydroxyvitamin-D3 (VitD) and sirtuin-1 (SIRT1) in mitigating pathological cardiac remodeling is well recognized. However, the potential for SIRT1 to mediate the inhibitory effects of VitD on angiotensin II (Ang II) -induced hypertrophy in H9c2 cardiomyoblasts remains unclear.MethodsH9c2 cardiomyoblasts were exposed to Ang II or a combination of VitD and Ang II, both in the absence and presence of SIRT1-specific siRNA. In each cell group, cell viability, hypertrophy, and redox state were evaluated using relevant techniques.ResultsIn H9c2 cells transfected with SIRT1 siRNA, VitD failed to significantly counteract the Ang II-induced perturbations, which included a reduction in cell viability, decreased CAT and SOD activity/mRNA levels, diminished MnSOD mRNA levels, and increased MDA content. Conversely, VitD significantly inhibited Ang II-induced hypertrophy in H9c2 cells by reducing cell size and lowering ANP and BNP mRNA levels, regardless of SIRT1 status. Notably, neither Ang II nor VitD altered the expression of SIRT1 mRNA or protein in H9c2 cells.ConclusionSIRT1 serves as an important regulator of pro-survival, but not anti-hypertrophic functions of VitD in hypertrophied cardiomyoblasts. Indeed, the absence of SIRT1 jeopardizes the capabilities of VitD to confer its pro-survival activity in H9c2 cells. Therefore, SIRT1-centered activating compounds may augment the protective effects of VitD, providing a promising therapeutic strategy to reduce the risk of cardiac hypertrophy and heart failure.Graphical abstractIn H9c2 cells, 1,25-dihydroxyvitamin-D3 (VitD3) fends off angiotensin II (Ang II) -induced hypertrophy, increased lipid peroxidation, reduced antioxidant enzymes, and diminished cell viability. SIRT1 knockdown (SIRT1 siRNA) does not interfere with the anti-hypertrophy effects of VitD, but it abrogates the protective actions of VitD on lipid peroxidation, antioxidant enzymes, and cell viability. Consequently, the loss of SIRT1 destroys the pro-survival activity of VitD in H9c2 cells