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健康的长寿相关蛋白质改善心脏功能在心肌病的小鼠模型与保存的喷射小部分心脏病变
Valeria Vincenza Alvino1, Sadie Slater1, Yan Qiu1
1Bristol Medical School, Translational Health Sciences, University of Bristol, Upper Maudlin St, Bristol, BS2 8HW, UK.
Cardiovascular diabetology
|November 5, 2024
概括
口服长寿相关变体 (LAV) 蛋白质BPIFB4在老化和糖尿病小鼠中改善了心脏功能. 这种蛋白质疗法有可能预防心脏功能障碍,尽管在糖尿病模型中,疗效因性别而异.
科学领域:
- 心血管生物学 心血管生物学
- 衰老研究研究 衰老研究
- 代谢性疾病 代谢性疾病
背景情况:
- 衰老和糖尿病是心力衰竭的危险因素,心脏衰竭的危险因素是保持喷射分数.
- 目前没有一种治疗方法可以预防老年人和糖尿病患者的心脏功能障碍.
- 之前的研究表明,单剂量LAV-BPIFB4基因在小鼠中阻止了心脏衰退.
研究的目的:
- 为了确定口服的LAV-BPIFB4蛋白是否复制了基因治疗所见的好处.
- 评估LAV-BPIFB4蛋白在老化和糖尿病小鼠模型中的疗效.
主要方法:
- 在老年C57BL/6J小鼠和糖尿病C57BLKS/J-Leprdb/Leprdb小鼠中进行了两项随机对照研究.
- 动物接受了口服LAV-BPIFB4蛋白 (3微克/动物每三天一次) 或载体30天.
- 心声扫描在基线和治疗后评估心脏功能;心脏被组织学分析.
主要成果:
- 在老年小鼠中,LAV-BPIFB4蛋白改善了心脏收缩性,毛细血管性,减少了纤维化和衰老.
- 在男性糖尿病小鼠中,治疗增强了缩功能,微血管密度,并减少了衰老.
- 治疗的益处仅限于雌性糖尿病小鼠的缩功能;没有观察到对体重或葡萄糖尿的影响.
结论:
- 口服LAV-BPIFB4蛋白在动物模型中可行且有效地减轻心脏功能障碍的风险因素.
- 性别影响了糖尿病小鼠中LAV-BPIFB4蛋白的治疗疗效.
- 这种蛋白质变体有望预防与年龄和糖尿病有关的心脏功能障碍.
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