Myocardial fatty acid metabolism and drug therapy in rats with heart failure.

心力衰竭大鼠心肌脂肪酸代谢和药物治疗。

• 批准号: 13670750
• 负责人: WATANABE Kenichi
• 金额: $ 2.62万
• 依托单位: Niigata university of Pharmacy and Applied Life Sciences
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670750/
• 关键词: Heart failure; Angiotensin converting enzyme inhibitor; β-blocker; Myocardial sympathetic denervation; Immuno-deficiency; Angiotensin-II receptor blockade; Ischemic heart disease; Fatty acid metabolism; 心筋炎; 遺伝子導入; 拡張型心筋症; CD36欠損症

Dilated cardiomyopathy is a set of heterogeneous diseases of left ventricular dysfunction of unknown etiology, which has a variety of clinical courses and pathological findings. Long-chain fatty acids are one of the major cardiac energy substrates, so, understanding long-chain fatty acid metabolism may help in elucidating the mechanisms of various heart diseases. Angiotensin(AT)-II receptor blockers (ARB) and angiotensin-converting enzyme inhibitors (ACEI) have been shown to reduce morbidity and mortality in patients with heart failure, but their inhibitory actions on AT-I-induced increases in blood pressure in heart failure are not clear. AT-I blocking and cardioprotective properties of the ARB candesartan and ACEI quinapril were studied in a rat model of dilated cardiomyopathy. Metaiodobenzylguanidine(MIBG) is a reliable marker for the detection of cardiac adrenergic neuronal damage in heart failure. The cardioprotective properties of carvedilol, a vasodilating β-adrenoceptor blocking agent, were studied in a rat model of dilated cardiomyopathy. Myocardial long-chain fatty acids metabolism was decreased in rats with heart failure. Although low-dose candesartan can block increases in blood pressure with circulating AT-I same to the extent as high-dose quinapril, it does not confer sufficient protection against injury from the rennin-angiotensin system in heart failure. Carvedilol has beneficial effects and protects cardiac adrenergic neurons in dilated cardiomyopathy.

扩张型心肌病是一组病因不明的左心室功能不全的异质性疾病，具有多种临床病程和病理表现。长链脂肪酸是主要的心脏能量底物之一，了解长链脂肪酸代谢有助于阐明各种心脏疾病的发生机制。血管紧张素(AT)-II受体阻滞剂（ARB）和血管紧张素转换酶抑制剂（ACEI）已被证明可以降低心力衰竭患者的发病率和死亡率，但它们对AT- i诱导的心力衰竭患者血压升高的抑制作用尚不清楚。在扩张型心肌病大鼠模型中研究了ARB坎地沙坦和ACEI喹普利的AT-I阻断和心脏保护作用。Metaiodobenzylguanidine（MIBG）是检测心力衰竭时心脏肾上腺素能神经元损伤的可靠标志物。用扩张型心肌病大鼠模型研究了血管舒张β-肾上腺素受体阻滞剂卡维地洛的心脏保护作用。心力衰竭大鼠心肌长链脂肪酸代谢降低。尽管低剂量坎地沙坦可以像高剂量喹奈普利一样阻断血液中AT-I引起的血压升高，但它不能提供足够的保护，防止心力衰竭时肾素-血管紧张素系统的损伤。卡维地洛在扩张型心肌病中具有保护心肌肾上腺素能神经元的作用。

项目成果

Improved synthesis of pure [18F] fluoro-compounds for PET studies from bromo-compounds.

改进了从溴化合物合成用于 PET 研究的纯 [18F] 氟化合物。

• 发表时间: 2003
• 期刊: Appl.Radiat.Isot. (in press)
• 作者: Takahashi T;Mizuno T;Ido T;Iwata R;Watanabe K.
• 通讯作者: Watanabe K.

Difference in CD22 molecules in human B cells and basophils.

人类 B 细胞和嗜碱性粒细胞中 CD22 分子的差异。

• 发表时间: 2002
• 期刊: Exp Hematology. 30
• 作者: Toba K;Hanawa H;Fuse I;Sakaue M;Watanabe K;Uesugi Y;Higuchi W;Takahashi M;Aizawa Y.
• 通讯作者: Aizawa Y.

Wen Juan, Watanabe K et al.: "Quinapril inhibits progression of heart failure and fibrosis in rats with dilated cardiomyopathy after myocarditis"Mol Cell Biochem. (in press). (2003)

Wen Juan，Watanabe K等：“喹那普利抑制心肌炎后扩张型心肌病大鼠心力衰竭和纤维化的进展”Mol Cell Biochem。

Fuse K, Watanabe K et al.: "Enhanced expression and production of monocyte chemoattractant protein-1 in myocarditis"Clin Exp Immunol.. 124. 346-352 (2001)

Fuse K、Watanabe K 等人：“心肌炎中单核细胞趋化蛋白-1 的表达和产生增强”Clin Exp Immunol.. 124. 346-352 (2001)

Ma M, Watanabe K et al.: "Inhibition of progression of heart failure and expression of TGF-β1 mRNA in rats with heart failure by the ACE inhibitor quinapril"J Cardiovascul Pharmacol. 38. S51-S54 (2001)

Ma M、Watanabe K 等人：“ACE 抑制剂喹那普利对心力衰竭大鼠的心力衰竭进展和 TGF-β1 mRNA 表达的抑制”J Cardioangio Pharmacol 38. S51-S54 (2001)。