Mechanisms of cardiac dysfunction in metabolic syndrome

1)肥胖大鼠心脏中硬脂酰辅酶A去饱和酶-1（stearoyl-CoA desaturase-1，SCD-1）表达增加可促进心肌脂质蓄积和代谢异常。因此，我们研究了心脏SCD 1的表达在肥胖大鼠诱导的富含蔗糖的饮食。实时荧光定量PCR结果显示，高糖饮食可显著增加大鼠心脏SCD 1 mRNA的表达。我们还通过免疫组织化学方法检测心肌细胞中SCD 1上调的蛋白表达。为了建立SCD 1和脂质代谢之间的关系，我们使用腺病毒制备SCD 1过表达的心肌细胞。SCD 1过表达显著增加了30%的甘油三酯在心肌细胞中的积累，并减少了58%的脂肪酸氧化。总之，我们的研究结果首次证明了SCD 1在内脏肥胖大鼠心脏中表达上调，而SCD 1在内脏肥胖大鼠心脏中过度表达。 ...更多信息 急性压力超负荷上调，慢性压力超负荷下调大鼠心脏细胞因子信号抑制因子-3（SOCS-3）的表达近年来的研究表明，SOCS-3可被血管紧张素II（Ang 1 T）快速诱导，并调节AngII信号。然而，SOCS-3在心血管疾病中的作用尚不清楚。因此，我们研究了SOCS-3 mRNA在压力超负荷大鼠心脏中的表达。北方印迹法显示，主动脉结扎后第1天，心脏SOCS-3 mRNA表达明显增加。有趣的是，与假手术大鼠相比，结扎后2周和4周大鼠中的SOCS-3表达显著降低。此外，24小时暴露于分离的新生大鼠心室肌细胞与AngII，TNF α或瘦素诱导不同的SOCS-3 mRNA的表达，但连续暴露这些生长因子48至72小时减少SOCS-3表达的时间依赖性。结论急性压力超负荷可上调心肌细胞SOCS-3的表达，SOCS-3可能作为负反馈系统抑制生长因子的信号转导。然而，慢性压力超负荷下调SOCS-3的表达。少

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