权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Mechanisms of cardiac dysfunction in metabolic syndrome

代谢综合征心功能障碍的机制

基本信息

批准号：
18590761
负责人：
YOKOYAMA Tomoyuki
金额：
$ 2.39万
依托单位：
Gunma University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2006
资助国家：
日本
起止时间：
2006 至 2007
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18590761/
关键词：
obesity stearoyl-CoA desaturase-1 fatty acid pressure overload Suppressor of cytokine signal-3 メタボリックシンドローム N-epsilon-(hexanol) lysine 酸化ストレス Suppressor of cytokine signal-3 心筋細胞

项目摘要

1) Increased stearoyl-CoA desaturase-1 (SCD-1) expression in obese rat heart enhances to myocardial lipid accumulation and metabolic abnormalityAlthough SCD1 is expressed in various tissues including heart, SCDI involvement in cardiovascular disease is poorly understood. We therefore examined the expression of cardiac SCD1 in obese rats which were induced by a sucrose-rich diet. Using Real-time PCR, SCD1 mRNAs expression was significantly increased in rat heart after sucrose-rich diet. We also detected protein expression of SCD1 up-regulation in cardiomyocytes by immunohistochemistry. To establish a relationship between SCD1 and lipid metabolism, we prepared SCD1 overexpressed cardiac myocytes using adenovirus. SCD1-overexpression significantly increased accumulation of triglyceride in myocytes by 30% and decreased fatty acid oxidation by 58%. In conclusions, our results demonstrated for the first time that SCD1 expression was up-regulated in visceral obese rat hearts and SCD1-overexpr … More ession led to excessive lipid accumulation and deterioration of fatty acid oxidation.2) Acute pressure overload up-regulates, but chronic pressure overload down-regulates Suppressor of cytokine signal-3 (SOCS-3) expression in rat heartRecent study showed that SOCS-3 was rapidly induced by angiotensinII (Ang1T) in heart and modulated AngII signaling. However, role of SOCS-3 in cardiovascular diseases has not been known. We therefore examined expression of SOCS-3 mRNA in pressure overloaded rat heart. One day after aortic banding, SOCS-3 mRNA expression in heart was markedly increased by Northern blotting. Interestingly, SOCS-3 expressions in rats 2 and 4 weeks after banding were significantly decreased in comparison with sham rats. Further, 24 hours exposure to isolated neonatal rat ventricular myocytes with AngII, TNFa or leptin induced distinct SOCS-3 mRNA expression, but continuous exposure of theses growth factors for 48 to 72 hours diminished SOCS-3 expression time-dependently. We conclude that acute pressure overload up-regulates SOCS-3 expression in cardiac myocytes, and SOCS-3 may inhibit signaling of growth factors as negative feedback system. However, chronic pressure overload down-regulates SOCS-3 expression. Less

1）肥胖大鼠心脏中硬脂酰辅酶A去饱和酶1（SCD-1）表达增加导致心肌脂质积累和代谢异常虽然SCD1在包括心脏在内的多种组织中表达，但SCDI与心血管疾病的关系尚不清楚。因此，我们检测了富含蔗糖饮食诱导的肥胖大鼠心脏 SCD1 的表达。使用实时 PCR，在富含蔗糖的饮食后，大鼠心脏中 SCD1 mRNA 的表达显着增加。我们还通过免疫组织化学检测了心肌细胞中 SCD1 上调的蛋白表达。为了建立SCD1和脂质代谢之间的关系，我们使用腺病毒制备了SCD1过表达的心肌细胞。 SCD1 过表达使肌细胞中甘油三酯的积累显着增加 30%，脂肪酸氧化减少 58%。总之，我们的结果首次证明内脏肥胖大鼠心脏中SCD1表达上调，并且SCD1过度表达导致脂质过度积累和脂肪酸氧化恶化。2）急性压力超负荷上调，但慢性压力超负荷下调大鼠心脏中细胞因子信号抑制因子3（SOCS-3）的表达。 SOCS-3 在心脏中被血管紧张素 II (Ang1T) 快速诱导并调节 AngII 信号传导。然而，SOCS-3在心血管疾病中的作用尚不清楚。因此，我们检测了压力超负荷大鼠心脏中 SOCS-3 mRNA 的表达。主动脉结扎后一天，Northern blotting显示心脏中SOCS-3 mRNA的表达显着增加。有趣的是，与假手术大鼠相比，在环扎后2周和4周的大鼠中SOCS-3的表达显着降低。此外，将分离的新生大鼠心室肌细胞暴露于AngII、TNFa或瘦素24小时可诱导明显的SOCS-3 mRNA表达，但连续暴露这些生长因子48至72小时可随时间依赖性减少SOCS-3表达。我们得出的结论是，急性压力超负荷上调心肌细胞中SOCS-3的表达，并且SOCS-3可能作为负反馈系统抑制生长因子的信号传导。然而，慢性压力超负荷会下调 SOCS-3 的表达。较少的