Repurposing of glatiramer acetate to treat cardiac ischemia in rodent models

IF 9.4 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Nature cardiovascular research Pub Date : 2024-08-26 DOI:10.1038/s44161-024-00524-x
Gal Aviel, Jacob Elkahal, Kfir Baruch Umansky, Hanna Bueno-Levy, Zachary Petrover, Yulia Kotlovski, Daria Lendengolts, David Kain, Tali Shalit, Lingling Zhang, Shoval Miyara, Matthias P. Kramer, Yifat Merbl, Stav Kozlovski, Ronen Alon, Rina Aharoni, Ruth Arnon, David Mishali, Uriel Katz, Dean Nachman, Rabea Asleh, Offer Amir, Eldad Tzahor, Rachel Sarig
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Abstract

Myocardial injury may ultimately lead to adverse ventricular remodeling and development of heart failure (HF), which is a major cause of morbidity and mortality worldwide. Given the slow pace and substantial costs of developing new therapeutics, drug repurposing is an attractive alternative. Studies of many organs, including the heart, highlight the importance of the immune system in modulating injury and repair outcomes. Glatiramer acetate (GA) is an immunomodulatory drug prescribed for patients with multiple sclerosis. Here, we report that short-term GA treatment improves cardiac function and reduces scar area in a mouse model of acute myocardial infarction and a rat model of ischemic HF. We provide mechanistic evidence indicating that, in addition to its immunomodulatory functions, GA exerts beneficial pleiotropic effects, including cardiomyocyte protection and enhanced angiogenesis. Overall, these findings highlight the potential repurposing of GA as a future therapy for a myriad of heart diseases. Sarig and Tzahor et al. show that the multiple sclerosis drug glatiramer acetate improves cardiac function and reduces scar area in rodent models of acute myocardial infarction and ischemic heart failure.

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在啮齿动物模型中重新利用醋酸格拉替雷治疗心肌缺血。
心肌损伤最终可能导致心室重塑不良和心力衰竭(HF),而心力衰竭是全球发病率和死亡率的主要原因。鉴于开发新疗法的速度缓慢且成本高昂,药物再利用是一种极具吸引力的选择。对包括心脏在内的许多器官进行的研究强调了免疫系统在调节损伤和修复结果方面的重要性。醋酸格拉替雷(GA)是一种用于多发性硬化症患者的免疫调节药物。在此,我们报告了在急性心肌梗塞小鼠模型和缺血性高频房颤大鼠模型中,GA 的短期治疗可改善心脏功能并减少瘢痕面积。我们提供的机理证据表明,除了免疫调节功能外,GA 还能产生有益的多效应,包括保护心肌细胞和增强血管生成。总之,这些发现凸显了 GA 作为未来治疗多种心脏疾病的一种疗法的潜在用途。
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