Inhibition of prolyl hydroxylase 3 ameliorates cardiac dysfunction in diabetic cardiomyopathy.
Inhibition of prolyl hydroxylase 3 ameliorates cardiac dysfunction in diabetic cardiomyopathy.
复制标题
脯氨酰羟化酶 3 的抑制可改善糖尿病心肌病的心功能障碍。
DOI：
10.1016/j.mce.2015.01.014
复制
发表时间：
2015
影响因子：
4.1
通讯作者：
An Fengshuang
中科院分区：
文献类型：
--
作者：
Xia Yanfei;Gong Luwei;Liu Hui;Luo Beibei;Li Bo;Li Rui;Li Beibei;Lv Mei;Pan Jinyu;An Fengshuang
脯氨酰羟化酶3（PHD 3）是脯氨酰羟化酶（PHDs）家族的成员，并且由缺氧诱导。它在调节缺氧诱导因子（HIF）的丰度方面起着关键作用。它在糖尿病大鼠心脏中的表达增加;然而，其作用仍不清楚。我们研究了PHD 3在糖尿病诱导的大鼠心肌功能障碍中的潜在作用和作用机制。在体内，通过高脂饮食和腹腔注射链脲佐菌素诱导2型糖尿病大鼠模型。在体外，原代新生心肌细胞和H9 c2成心肌细胞在33.3 mM葡萄糖（高糖，HG）和5.5 mM葡萄糖（正常葡萄糖，NG）中培养，后者用作对照。利用PHD 3-siRNA抑制PHD 3的表达，探讨PHD 3在HG诱导的H9 c2心肌细胞凋亡中的作用。糖尿病心肌病（DCM）大鼠左心室功能不全，心肌细胞凋亡和纤维化。PHD 3在糖尿病大鼠心肌组织中表达增加，抑制PHD 3可改善糖尿病大鼠心肌组织的病理改变。此外，抑制PHD 3显著降低HG诱导的H9 c2成心肌细胞凋亡和MAPK激活。我们的研究结果表明，PHD 3抑制改善糖尿病性心肌病患者的心肌功能障碍。
Prolyl hydroxylase 3 (PHD3) is a member of the prolyl hydroxylases (PHDs) family and is induced by hypoxia. It plays a critical role in regulating the abundance of hypoxia-inducible factor (HIF). Its expression is increased in diabetic rat hearts; however, its role remains unclear. We investigated the potential role and mechanism of action of PHD3 in the setting of diabetes-induced myocardial dysfunction in rats.In vivo, type 2 diabetic rat model was induced via a high-fat diet and intraperitoneal injection of streptozotocin. PHD3 expression was knocked down using lentivirus-mediated short-hairpin RNA (shRNA).In vitro, primary neonatal cardiomyocytes and H9c2 cardiomyoblasts were cultured in 33.3 mM glucose (high glucose, HG) and 5.5 mM glucose (normal glucose, NG), the latter of which was used as a control. PHD3-siRNA was used to inhibit the expression of PHD3 and to investigate the role of PHD3 in HG-induced apoptosis in H9c2 cardiomyoblasts. Rats with diabetic cardiomyopathy (DCM) exhibited severe left ventricular dysfunction as well as myocardial apoptosis and fibrosis. PHD3 expression was increased in the myocardial tissues of diabetic rats, and inhibition of PHD3 ameliorated the disease. Additionally, the inhibition of PHD3 significantly decreased HG-induced apoptosis and MAPK activation in H9c2 cardiomyoblasts. Our results suggest that PHD3 inhibition ameliorates myocardial dysfunction in the setting of diabetic cardiomyopathy.