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表皮生长因子受体的骨髓细胞特异性缺失加剧了急性心脏损伤
Ama D Okyere1, Tapas K Nayak1, Viren Patwa1
1Center for Translational Medicine, Lewis Katz School of Medicine, Temple University, Philadelphia, PA 19140, U.S.A.
Clinical science (London, England : 1979)
|September 20, 2023
概括
骨髓细胞中表皮生长因子受体 (EGFR) 的损失使心脏病发作后的心脏修复恶化. 骨髓细胞特异性EGFR淘汰小鼠显示心脏功能受损,心肌梗塞后愈合减少.
科学领域:
- 心血管生物学 心血管生物学
- 免疫学 免疫学 免疫学
- 分子医学是分子医学.
背景情况:
- 骨髓状细胞,包括巨细胞,对于应对心脏损伤至关重要.
- 表皮生长因子受体 (EGFR) 影响某些疾病中的巨细胞反应,但其在心脏损伤中的作用尚不清楚.
研究的目的:
- 研究骨髓细胞特异性EGFR在心脏功能和心肌梗塞 (MI) 后重塑中的作用.
主要方法:
- 通过将混合EGFR小鼠与LysM-Cre转基因小鼠进行繁殖,生成骨髓特异性EGFR淘汰赛 (mKO) 的小鼠.
- 评估心脏结构和功能使用心声回声学,免疫组织化学,RNA测序和流细胞计在基线和后MI.
- 分析了对基因表达变化的心脏Cd11b+髓质细胞.
主要成果:
- 骨髓特异性EGFR缺失导致了基线心肌细胞缩.
- RNA测序揭示了转基因细胞转录的改变,这表明新血管化减少.
- 在心脏病发作后,mKO小鼠表现出更快的心脏功能下降,增高缩,毛细血管密度下降.
- 在MI后的mKO髓质细胞中,支持修复的媒介Vegfa和Il10的含量下降.
结论:
- 骨髓细胞中EGFR的损失会改变心脏内存的巨细胞,导致基底压力.
- 骨髓细胞中的EGFR缺乏会加剧心脏功能障碍,并损害急性缺血性损伤后的修复.
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