Sirt (Sirtuin) 7, the most recently identified mammalian sirtuin, has been shown to contribute to appropriate wound healing processes after acute cardiovascular insult. However, its role in the development of cardiac remodeling after pressure overload is unclear. Cardiomyocyte-specific Sirt7-knockout and control mice were subjected to pressure overload induced by transverse aortic constriction. Cardiac hypertrophy and functions were then examined in these mice. Sirt7 protein expression was increased in myocardial tissue after pressure overload. Transverse aortic constriction-induced increases in heart weight/tibial length were significantly augmented in cardiomyocyte-specific Sirt7-knockout mice compared with those of control mice. Histological analysis showed that the cardiomyocyte cross-sectional area and fibrosis area were significantly larger in cardiomyocyte-specific Sirt7-deficient mice. Cardiac contractile functions were markedly decreased in cardiomyocyte-specific Sirt7-deficient mice. Mechanistically, we found that Sirt7 interacted directly with GATA4 and that the exacerbation of phenylephrine-induced cardiac hypertrophy by Sirt7 knockdown was decreased by GATA4 knockdown. Sirt7 deacetylated GATA4 in cardiomyocytes and regulated its transcriptional activity. Interestingly, we demonstrated that treatment with nicotinamide mononucleotide, a known key NAD+ intermediate, ameliorated agonist-induced cardiac hypertrophies in a Sirt7-dependent manner in vitro. Sirt7 deficiency in cardiomyocytes promotes cardiomyocyte hypertrophy in response to pressure overload. Sirt7 exerts its antihypertrophic effect by interacting with and promoting deacetylation of GATA4.

中文翻译：

---

心肌细胞 Sirt (Sirtuin) 7 通过与 GATA4 相互作用和去乙酰化来改善压力诱导的心脏肥大

Sirt (Sirtuin) 7 是最近发现的哺乳动物 Sirtuin，已被证明有助于急性心血管损伤后的适当伤口愈合过程。然而，其在压力超负荷后心脏重塑发展中的作用尚不清楚。心肌细胞特异性 Sirt7 基因敲除小鼠和对照小鼠承受由横向主动脉收缩引起的压力超负荷。然后在这些小鼠中检查心脏肥大和功能。压力超负荷后心肌组织中的Sirt7蛋白表达增加。与对照小鼠相比，在心肌细胞特异性 Sirt7 基因敲除小鼠中，横向主动脉收缩引起的心脏重量/胫骨长度增加显着增加。组织学分析表明，心肌细胞特异性 Sirt7 缺陷小鼠的心肌细胞横截面积和纤维化面积显着较大。心肌细胞特异性 Sirt7 缺陷小鼠的心脏收缩功能显着降低。从机制上讲，我们发现 Sirt7 直接与 GATA4 相互作用，并且通过 GATA4 敲低减少了由 Sirt7 敲低引起的去氧肾上腺素诱导的心脏肥大的恶化。Sirt7 使心肌细胞中的 GATA4 脱乙酰化并调节其转录活性。有趣的是，我们证明了用烟酰胺单核苷酸（一种已知的关键 NAD+ 中间体）治疗在体外以 Sirt7 依赖性方式改善了激动剂诱导的心脏肥大。心肌细胞中的 Sirt7 缺乏可促进心肌细胞肥大以应对压力超负荷。