Astani Akram, Maroofi Abdulbaset, Hekmatimoghaddam Seyedhossein, Sarebanhassanabadi Mohammadtaghi, Safari Fatemeh
Department of Microbiology, Faculty of Medicine, Shahid Sadoughi University of Medical Sciences, Yazd, Iran.
Department of Exercise Physiology, University of Guilan, Rasht, Iran.
Mol Biol Rep. 2024 Dec 31;52(1):96. doi: 10.1007/s11033-024-10168-6.
The 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.
H9c2 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.
In 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.
SIRT1 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.
1,25 - 二羟基维生素D3（VitD）和沉默调节蛋白1（SIRT1）在减轻病理性心脏重塑中的作用已得到充分认识。然而，SIRT1介导VitD对血管紧张素II（Ang II）诱导的H9c2心肌成纤维细胞肥大的抑制作用的潜力仍不清楚。
将H9c2心肌成纤维细胞暴露于Ang II或VitD与Ang II的组合中，同时存在和不存在SIRT1特异性小干扰RNA（siRNA）。在每个细胞组中，使用相关技术评估细胞活力、肥大和氧化还原状态。
在转染了SIRT1 siRNA的H9c2细胞中，VitD未能显著抵消Ang II诱导的扰动，这些扰动包括细胞活力降低、CAT和SOD活性/ mRNA水平降低、MnSOD mRNA水平降低以及MDA含量增加。相反，无论SIRT1状态如何，VitD通过减小细胞大小和降低ANP和BNP mRNA水平，显著抑制H9c2细胞中Ang II诱导的肥大。值得注意的是，Ang II和VitD均未改变H9c2细胞中SIRT1 mRNA或蛋白质的表达。
SIRT1是肥大心肌成纤维细胞中VitD促生存功能的重要调节因子，但不是抗肥大功能的调节因子。事实上，SIRT1的缺失危及VitD在H9c2细胞中赋予其促生存活性的能力。因此，以SIRT1为中心的激活化合物可能增强VitD的保护作用，为降低心脏肥大和心力衰竭风险提供一种有前景的治疗策略。
