减少胰岛素揭示了VEGFB对心脏基质利用的新效应
Rui Shang1, Chae Syng Lee1, Hualin Wang1
1Faculty of Pharmaceutical Sciences (R.S., C.S.L., H.W., B.H., B.R.), University of British Columbia, Vancouver.
Arteriosclerosis, thrombosis, and vascular biology
|December 27, 2023
概括
血管内皮生长因子B (VEGFB) 增强心脏脂肪酸从脂蛋白中吸收,防止脂质积累. 糖尿病中VEGFB作用的丧失有助于代谢不灵活性和心脏功能障碍.
科学领域:
- 心血管生物学 心血管生物学
- 代谢调节 代谢调节 代谢调节 代谢调节
- 分子心脏病学分子心脏病学
背景情况:
- 心脏主要使用外部脂肪酸 (FA) 作为能量.
- 血管内皮生长因子B (VEGFB) 增强了内皮FA的吸收.
- VEGFB在脂蛋白脂酶 (LPL) 介导的心脏FA供应中的作用尚不清楚.
研究的目的:
- 调查VEGFB在调节心脏FA代谢,特别是LPL活性中的作用.
- 评估VEGFB对心脏FA吸收和体内氧化的影响.
- 在糖尿病的背景下探索VEGFB的潜在心脏保护作用.
主要方法:
- 产生具有心肌细胞特异性过度表达的VEGFB转基因 (Tg) 鼠.
- 使用Langendorff穿透心脏测量冠状动脉LPL活动.
- 通过PET成像,使用放射性标记的标记物进行体内心脏FA吸收评估.
- 使用高分辨率呼吸计评估线粒体FA氧化.
- 使用链毒素诱导糖尿病,并监测心脏功能.
主要成果:
- 过度表达VEGFB导致细胞内LPL在心肌细胞中的积累.
- 禁食诱导的胰岛素缺乏促进了VEGFB介导的LPL转位和增加冠状动脉LPL活性.
- VEGFB增加了心脏从脂蛋白中吸收FA,促进线粒体氧化,防止心脏脂质积累.
- 糖尿病损害了Tg心脏中的VEGFB表达和信号传递,降低了其心脏保护作用.
结论:
- 在供应和利用来自LPL的FA方面,VEGFB发挥着新的作用.
- 糖尿病中VEGFB功能的丧失可能导致代谢不灵活性,脂毒性和糖尿病心肌病.
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