Analysis of metabolic remodeling and mitochondrial function in heart failure

心力衰竭代谢重塑和线粒体功能分析

• 批准号: 24790790
• 负责人: KATO Takao
• 金额: $ 2万
• 依托单位: The Tazuke Kofukai
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2012
• 资助国家: 日本
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-24790790/
• 关键词: ミトコンドリア; ミトコンドリア機能; 悪液質; 非侵襲的評価; 心不全; 解糖系; 骨格筋; 非侵襲的評価法

Although mitochondria play pivotal roles in heart failure, there are few feasible methods for cardiac assessing mitochondrial function in vivo. We validated that the retention of technetium-99m sestamibi (99mTc-MIBI) is useful for assessing cardiac mitochondrial function in vivo and that increased washout (or decreased retention) of 99mTc-MIBI occurs in an animal model of HF and patients with HF, associated with the severity of the disease.Next, we examined the effects of persistent overexpression of phosphoglycerate mutase 2 (Pgam2), a glycolytic enzyme, on cardiac energy metabolism and function. The uptake of analogs of glucose or fatty acids and the phosphocreatine/ATP ratio at rest were normal. The levels of metabolites in the initial few steps of glycolysis and lactate remained unchanged. The levels of metabolites in the tricarboxylic acid (TCA) cycle were altered, and the capacity of mitochondrial function was decreased.

虽然线粒体在心力衰竭中起着关键作用，但目前尚无可行的方法在体内评估线粒体的功能。我们验证了99mTC-MIBI在活体心肌线粒体功能评估中的滞留是有用的，在心力衰竭和心力衰竭患者的动物模型中，99mTC-MIBI的存留增加(或减少)与疾病的严重程度有关。接下来，我们研究了糖酵解酶磷酸甘油变位酶2(PGam2)持续过表达对心脏能量代谢和功能的影响。静息状态下葡萄糖或脂肪酸类似物的摄取和磷酸肌酸/三磷酸腺苷的比率是正常的。糖酵解和乳酸最初几个步骤的代谢物水平保持不变。三羧酸(TCA)循环中代谢产物水平发生改变，线粒体功能能力下降。

项目成果

Tc-99m Sestamibi washout is a useful method to assess cardiac mitochondrial function and the increased risk of a failing heart: a translational approach to understand the metabolic state of the heart.

Tc-99m Sestamibi 冲洗是评估心脏线粒体功能和心脏衰竭风险增加的有用方法：一种了解心脏代谢状态的转化方法。

• 发表时间: 2012
• 作者: Kato T;Shioi T;Kawamoto A;Kimura T;Nagakura D;Nakane E;Miyamoto S;Izumi T;Haruna T;Inoko T;Nohara R.
• 通讯作者: Nohara R.

Analysis of liver metabolism in a rat model of heart failure

• DOI: 10.1016/j.ijcard.2011.07.056
• 发表时间: 2012-11-29
• 期刊: INTERNATIONAL JOURNAL OF CARDIOLOGY
• 影响因子: 3.5
• 作者: Kato, Takao;Niizuma, Shinichiro;Shioi, Tetsuo
• 通讯作者: Shioi, Tetsuo

Mitochondrial function as a potential mediator of metabolic remodeling in the heart

线粒体功能作为心脏代谢重塑的潜在介质

• 发表时间: 2012
• 作者: Kato T;Shioi T;Kawashima T;Kawamoto A;Kimura T.
• 通讯作者: Kimura T.

Tc-99m Sestamibi washout is a useful method to assess cardiac mitochondrial function and the increased risk of a failing heart

Tc-99m Sestamibi 冲洗是评估心脏线粒体功能和心力衰竭风险增加的有用方法

• 发表时间: 2012
• 作者: Kato T;Shioi T;Kawashima T;Kawamoto A;Kimura T.;Takao Kato
• 通讯作者: Takao Kato

Abnormal liver metabolism and pro-inflammatory responses are modulators of cardiac cachexia in a rat model of heart failure

异常的肝脏代谢和促炎症反应是心力衰竭大鼠模型中心脏恶病质的调节剂

• 发表时间: 2013
• 期刊: J Cachexia Sarcopenia Muscle
• 作者: Kato T;Shioi T
• 通讯作者: Shioi T