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Development and Establishment of a New Therapeutic Strategy for Chronic Heart Failure due to Adenosine.

腺苷引起的慢性心力衰竭新治疗策略的开发和建立。

基本信息

批准号：
10557068
负责人：
KITAKAZE Masafumi
金额：
$ 7.49万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

We have previously revealed that adenosine mediates cardioprotection against ischemic and reperfusion injury. In the present study, we have been investigating the role of adenosine in ischemic and non- ischemic heart diseases from the basic and clinical aspects.First of all, we tested the gene expression in the ischemic and non- ischemic heart failure and we tested the role of adenosine in the gene expression. This is because it is important to know the pathophysiology of ischemic hearts to protect the hearts against ischemic and reperfusion injury. However, many cardiologists have investigated only a few substances once using Northern or Western blot analysis to clarify the pharmacological effect on the diseased hearts. However, many substances simultaneously contribute to the pathophysiology of diseased hearts. cDNA array technique has recently developed as a novel method to evaluate much gene expression at once. We performed cDNA array to examine how many and what kind of genes are … More changed in the diseased hearts using cDNA array with and without administration of an adenosine receptor inhibitor. Cardiac expression of many genes was regulated by ischemic, mechanical and neurohumoral stress. Endogenous adenosine modulated almost half of these regulated genes in the ischemic hearts.Second, we evaluated the effect of ATP, a precursor of adenosine, to limit the infarct size in the patients with acute myocardial infarction. Intracoronary injection of ATP was revealed to limit the infarct size.Third, we investigated the role of adenosine in chronic heart failure because chronic heart failure is the final common end- stage of cardiovascular diseases. We evaluated the process of induction of ecto- 5' -nucleotidase during the development of heart failure with the heart failure model of Syrian Hamster. At the compensatory period of chronic heart failure ecto- 5' -nucleotidase activity is enhanced, but ecto- 5'- nucleotidase activity was decreased in decompensated heart failure.Taken together, we have revealed that adenosine potently attenuates ischemic and non- ischemic heart failure, which may propose a new paradigm for the adenosine therapy of chronic heart failure. Less

我们之前已经发现腺苷介导心脏对缺血和再灌注损伤的保护作用。在本研究中，我们从基础和临床两方面探讨了腺苷在缺血性和非缺血性心脏病中的作用。首先，我们检测了缺血性和非缺血性心力衰竭的基因表达，并检测了腺苷在基因表达中的作用。这是因为了解缺血心脏的病理生理对保护心脏免受缺血和再灌注损伤是非常重要的。然而，许多心脏病学家只研究了少数物质，一旦使用北方或西方印迹分析来阐明对患病心脏的药理作用。然而，许多物质同时参与患病心脏的病理生理。cDNA阵列技术是近年来发展起来的一种同时检测多种基因表达的新方法。我们使用cDNA阵列来检测有多少和什么样的基因在患病心脏中发生了更多的变化，使用cDNA阵列和不使用腺苷受体抑制剂。心脏许多基因的表达受到缺血、机械和神经体液应激的调控。内源性腺苷调节了缺血性心脏中几乎一半的这些受调节基因。其次，我们评估了腺苷前体ATP在急性心肌梗死患者中限制梗死面积的作用。冠状动脉内注射ATP可限制梗死面积。第三，我们研究了腺苷在慢性心力衰竭中的作用，因为慢性心力衰竭是心血管疾病的最后常见终末期。我们利用叙利亚仓鼠心力衰竭模型，评价体外泌肽- 5′-核苷酸酶在心力衰竭发生过程中的诱导作用。慢性心力衰竭代偿期ecto- 5′-核苷酸酶活性增强，失代偿期ecto- 5′-核苷酸酶活性降低。综上所述，我们已经发现腺苷能有效地减轻缺血性和非缺血性心力衰竭，这可能为慢性心力衰竭的腺苷治疗提供一个新的范例。少