Novel Agonists of Adenosine Receptors in Animal Model of Acute Myocardial Infarction.

IF 4.7 2区医学 Q1 CHEMISTRY, MEDICINAL

Drug Design, Development and Therapy Pub Date : 2024-11-15 eCollection Date: 2024-01-01 DOI:10.2147/DDDT.S464712

Fabricio Beltrame, Bianca Nascimento-Carlos, Jaqueline S da Silva, Rodolfo Couto Maia, Tadeu Lima Montagnoli, Eliezer J Barreiro, Gisele Zapata-Sudo

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引用次数: 0

Abstract

Background and purpose: Current treatments for acute myocardial infarction (AMI) include pain relief and attempts to improve survival. This study investigated the effects of two new ligands of the adenosine receptor, LASSBio-1027 and LASSBio-1860, on cardiac function in an experimental model of AMI.

Methods: AMI was induced in Wistar rats by ligating the anterior descending coronary arteries. Infarcted animals were treated orally with vehicle (DMSO), LASSBio-1027 (30 and 70 μmol/kg), or LASSBio-1860 (70 μmol/kg) for seven days. Hemodynamic parameters were observed using echocardiography, whereas inflammation and fibrosis were detected using histological analysis.

Results: MI increased the filling pressure from 23.0 ± 1.6 and 14.0 ± 2.0 to 37.0 ± 3.7 and 33.2 ± 8.0, respectively indicating diastolic dysfunction. However, treatment with LASSBio-1027 (70 μmol/kg) and LASSBio-1860 (70 μmol/kg) reduced this parameter to 23.9 ± 5.4 and 17.1 ± 6.7. An impairment in ejection fraction from 57.1 ± 3.2 to 36.6 ± 2.0% was observed after MI, partially recovered to 47.0 ± 7.4% by LASSBio-1027 and fully restored to 61.8 ± 4.3% after 7 days of treatment with LASSBio-1860. After MI, collagen deposition in LV free wall was increased to 31.4 ± 11.0% and treatment with LASSBio-1027 reduced to 23.4 ± 6.0 and 19.7 ± 8.0% at 30 and 70 μmol/kg, respectively. Similarly, LASSBio-1860 reduced collagen levels to 63.1 ± 2.0%.

Conclusion: Fibrosis and inflammatory components of MI reduced following treatment with agonist of adenosine receptor subtype A2A. Cardiac remodeling induced by LASSBio-1027 and LASSBio-1860 may be responsible for the improvement in cardiac function in AMI through the activation of A2A adenosine receptors.

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急性心肌梗死动物模型中腺苷受体的新型激动剂

背景和目的：目前治疗急性心肌梗死（AMI）的方法包括缓解疼痛和提高存活率。本研究调查了腺苷受体的两种新配体 LASSBio-1027 和 LASSBio-1860 在急性心肌梗死实验模型中对心脏功能的影响：方法：通过结扎前降支冠状动脉诱发 Wistar 大鼠急性心肌梗死。用载体（DMSO）、LASSBio-1027（30 和 70 μmol/kg）或 LASSBio-1860（70 μmol/kg）对梗死动物进行为期七天的口服治疗。用超声心动图观察血流动力学参数，用组织学分析检测炎症和纤维化：结果：心肌梗死使充盈压分别从 23.0 ± 1.6 和 14.0 ± 2.0 升至 37.0 ± 3.7 和 33.2 ± 8.0，表明舒张功能障碍。然而，使用LASSBio-1027（70 μmol/kg）和LASSBio-1860（70 μmol/kg）治疗后，该参数分别降至23.9 ± 5.4和17.1 ± 6.7。心肌梗死后，射血分数从 57.1 ± 3.2% 降至 36.6 ± 2.0%，LASSBio-1027 治疗后部分恢复至 47.0 ± 7.4%，LASSBio-1860 治疗 7 天后完全恢复至 61.8 ± 4.3%。心肌梗死后，左心室游离壁的胶原沉积增加到 31.4 ± 11.0%，使用 LASSBio-1027 治疗后，30 μmol/kg 和 70 μmol/kg 的胶原沉积分别减少到 23.4 ± 6.0% 和 19.7 ± 8.0%。同样，LASSBio-1860 可将胶原蛋白水平降至 63.1 ± 2.0%：结论：使用腺苷受体亚型 A2A 激动剂治疗后，心肌梗死的纤维化和炎症成分减少。LASSBio-1027和LASSBio-1860诱导的心脏重塑可能是通过激活A2A腺苷受体改善急性心肌梗死患者心脏功能的原因。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Design, Development and Therapy CHEMISTRY, MEDICINAL-PHARMACOLOGY & PHARMACY

CiteScore

9.00

自引率

0.00%

发文量

382

审稿时长

>12 weeks

期刊介绍： Drug Design, Development and Therapy is an international, peer-reviewed, open access journal that spans the spectrum of drug design, discovery and development through to clinical applications. The journal is characterized by the rapid reporting of high-quality original research, reviews, expert opinions, commentary and clinical studies in all therapeutic areas. Specific topics covered by the journal include: Drug target identification and validation Phenotypic screening and target deconvolution Biochemical analyses of drug targets and their pathways New methods or relevant applications in molecular/drug design and computer-aided drug discovery* Design, synthesis, and biological evaluation of novel biologically active compounds (including diagnostics or chemical probes) Structural or molecular biological studies elucidating molecular recognition processes Fragment-based drug discovery Pharmaceutical/red biotechnology Isolation, structural characterization, (bio)synthesis, bioengineering and pharmacological evaluation of natural products** Distribution, pharmacokinetics and metabolic transformations of drugs or biologically active compounds in drug development Drug delivery and formulation (design and characterization of dosage forms, release mechanisms and in vivo testing) Preclinical development studies Translational animal models Mechanisms of action and signalling pathways Toxicology Gene therapy, cell therapy and immunotherapy Personalized medicine and pharmacogenomics Clinical drug evaluation Patient safety and sustained use of medicines.