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Compounds for treatment of ischemic injury

A technology for compounds and ischemic attacks, applied in drug combinations, organic active ingredients, cardiovascular system diseases, etc., can solve the problems of not checking the potential role of miRNA, not during ischemia-reperfusion period, and not involving the protective effect of miRNA

Active Publication Date: 2014-09-17
PHARMAHUNGARY 2000
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Problems solved by technology

No data on miRNA regulation were reported during pre- or post-conditioning, however, neither during or immediately after ischemia-reperfusion
[0028] These publications generally consider late upregulation of miRNAs after infarction, usually days after the onset of ischemia or their experimental mimics, and do not address the cytoprotective role of miRNAs in acute ischemia-reperfusion injury, and the authors did not examine cellular Potential role of miRNAs in protection

Method used

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  • Compounds for treatment of ischemic injury
  • Compounds for treatment of ischemic injury
  • Compounds for treatment of ischemic injury

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specific Embodiment

[0324] Recently, the heart has been shown to have an extraordinary ability to adapt to ischemia-reperfusion stress, and in ischemia-reperfusion, this molecular plasticity of the heart has been the focus of intense research in anticipation that the underlying mechanisms could be applied therapeutically Sexual development. Ischemic preconditioning is a well-described adaptive response in which brief exposure to ischemia significantly increases the heart's ability to withstand subsequent ischemic injury. In addition, the application of short-term ischemia-reperfusion following prolonged ischemia also conferred cardioprotection from myocardial ischemia-reperfusion, a phenomenon known as ischemic postconditioning.

[0325] The discovery of these two major forms of endogenous anti-ischemia, cardioprotective mechanisms, has led to the development of new modalities for protecting ischemic and / or reperfused myocardium, and details the Our understanding of the molecular basis of injury...

Embodiment 1

[0471] Identification of miRNAs involved in ischemia-reperfusion injury

[0472] To identify miRNAs involved in ischemia-reperfusion injury, pre- and post-processed miRNAs were isolated from the anterior wall of the left ventricle 2 hours after reperfusion. Relative changes in miRNA expression following ischemia-reperfusion were determined using a time-matched control group as a baseline. Approximately 150 of the total 350 rat miRNAs studied were shown to be expressed in response to ischemia-reperfusion. We determined the microarray data by the expression of a randomly selected set of 17 miRNAs measured by QRT-PCR. Changes in expression of 15 miRNAs were confirmed by QRT-PCR (Table 2).

[0473] To demonstrate whether cardioprotective adaptive effects lead to altered miRNA profiles in the myocardium, ischemic preconditioning and postconditioning-induced miRNA expression levels were compared with non-ischemia time-matched controls or non-treated ischemia-reperfusion groups or ...

Embodiment 2

[0477] Identification of cardioprotective miRNAs involved in ischemic preconditioning and postconditioning

[0478] We considered miRNAs to be associated with ischemic preconditioning when the preconditioning assay resulted in a significant attenuation or significant enhancement of the ischemia-reperfusion effect on miRNA expression. These miRNAs included those in which preconditioning induced significant changes in miRNA expression when compared to non-ischemia time-matched controls and untreated ischemia-reperfusion groups (miRNA-139-3p, 139-5p, 188, 192, Shaded bars in figure; see e.g. Figure 5 ). miRNAs significantly altered by ischemia-reperfusion and miRNAs significantly reversed by pretreatment were also assigned to this category (miRNA-320; Figure 3A). Changes in this group of miRNAs likely contribute to the formation of preconditioning-induced cardioprotection. The direction of change observed under preconditioning compared to ischemia-reperfusion indicates whethe...

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Abstract

The present invention relates to microRNA (miRNA) compounds for use in the treatment of consequences of acute ischemia / reperfusion, a method for preparing miRNA compounds by using test ischemia-reperfusion, test preconditioning and test postconditioning of biological samples, use of the miRNA compounds in the preparation of pharmaceutical compositions having cytoprotective and / or anti-ischemic effect in ischemic cardiac diseases.

Description

technical field [0001] The present invention relates to a method for preparing specific microRNA (miRNA) compounds by detecting ischemia-reperfusion, detecting biological sample pretreatment and detecting biological sample post-treatment, for the prevention and / or treatment of cells or tissues to protect them from immunity miRNA compounds for the effects of acute ischemia-reperfusion injury in patients susceptible to ischemia or ischemic attack, and pharmaceutical compositions comprising them, and also miRNA compounds and nucleotides encoding them for use in diagnosis and in the manufacture of medicaments Uses in compositions, and methods for treating patients in need of protection of cells or tissues from acute ischemia-reperfusion injury. Background technique [0002] microRNA [0003] MicroRNAs (miRNAs) are small (about 18 to about 25 nucleotides in length, preferably 19-23 nucleotides in length) non-protein-coding RNA molecules that are currently considered to be the e...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12N15/113A61P9/10A61K31/7088A61K31/713
CPCC12N2310/113C12N2310/141A61K31/713C12N15/113A61P9/10
Inventor 彼得·费迪南德佐尔坦·沃尔高塔马斯·坎森特阿尼哥·戈尔比
Owner PHARMAHUNGARY 2000
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