Chen Shuzhen, Polaki Venkata, Bihl Ji C, Wang Jinju
Department of Biomedical Sciences, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV, United States.
Department of Pharmacology and Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH, United States.
Front Stroke. 2022;1:1015463. doi: 10.3389/fstro.2022.1015463. Epub 2022 Oct 13.
We have previously demonstrated that endothelial progenitor cell (EPC) derived exosomes (EPC-EXs) can protect endothelial cells (ECs) against hypoxia injury. Given that EX function varies upon the cellular status and EPC function is declined in hypertension, we speculate the function of EPC-EXs is altered in hypertension-ischemia conditions. Here, we studied the EPC-EX mediated communications of EPCs with ECs in hypertension-ischemia conditions. EPC-EXs were prepared from the bone marrow EPCs of wild-type (WT) and hypertensive renin transgene (R+) mice (WT-EPC-EXs and R-EPC-EXs, respectively). To mimic hypertension-ischemia injury, ECs were challenged with angiotensin II (Ang II; 10 M) plus hypoxia (1% O for 6 h) and reoxygenation (21% O for 24 h). To determine the function of EPC-EXs, ECs were co-cultured with EXs during the reoxygenation period. EX uptake effciency, EC viability, and angiogenic function were assessed. We found that: (1) The incorporation effciency of R-EPC-EXs by ECs was significantly decreased compared to the WT-EPC-EXs. (2) Ang II plus hypoxia reoxygenation-injured ECs displayed decreased cell viability, increased cell apoptosis, and compromised angiogenic ability, which were alleviated by R-EPC-EXs. (3) WT-EPC-EXs elicited better effects than R-EPC-EXs on protecting ECs from hypertension plus hypoxia injury. In conclusion, our data have demonstrated that EPC-EXs mediated communication of EPCs and ECs is compromised in hypertension-ischemia conditions, suggesting that impairment of EPC exosomal communication might contribute to the exaggerated cerebral ischemia injury in hypertension-associated ischemic stroke.
我们先前已证明，内皮祖细胞（EPC）衍生的外泌体（EPC-EXs）可保护内皮细胞（ECs）免受缺氧损伤。鉴于外泌体功能随细胞状态而异，且高血压时EPC功能下降，我们推测高血压-缺血状态下EPC-EXs的功能会发生改变。在此，我们研究了高血压-缺血状态下EPC-EXs介导的EPC与EC之间的通讯。EPC-EXs分别从野生型（WT）和高血压肾素转基因（R+）小鼠的骨髓EPC中制备（分别为WT-EPC-EXs和R-EPC-EXs）。为模拟高血压-缺血损伤，用血管紧张素II（Ang II；10 μM）加缺氧（1% O₂ 6小时）和复氧（21% O₂ 24小时）刺激ECs。为确定EPC-EXs的功能，在复氧期将ECs与外泌体共培养。评估外泌体摄取效率、EC活力和血管生成功能。我们发现：（1）与WT-EPC-EXs相比，ECs对R-EPC-EXs的摄取效率显著降低。（2）Ang II加缺氧复氧损伤的ECs显示细胞活力下降、细胞凋亡增加和血管生成能力受损，而R-EPC-EXs可缓解这些情况。（3）WT-EPC-EXs在保护ECs免受高血压加缺氧损伤方面比R-EPC-EXs产生更好的效果。总之，我们的数据表明，高血压-缺血状态下EPC-EXs介导的EPC与EC之间的通讯受损，提示EPC外泌体通讯受损可能导致高血压相关性缺血性卒中时脑缺血损伤加重。
