Shafeeque Chathathayil M, Harmanci Arif O, Thomas Sithara, Dienel Ari C, McBride Devin W, Peeyush Kumar T, Blackburn Spiros L
The Vivian L. Smith Department of Neurosurgery, University of Texas Health Science Center at Houston, Houston, TX, United States.
D. Bradley McWilliams School of Biomedical Informatics, University of Texas Health Science Center, Fannin, TX, United States.
Front Physiol. 2025 Apr 3;16:1529113. doi: 10.3389/fphys.2025.1529113. eCollection 2025.
Subarachnoid hemorrhage (SAH), characterized by the presence of hemoglobin (Hb) in the subarachnoid space, significantly impacts cerebral vessels, leading to various pathological outcomes. The toxicity of cell-free Hb released from erythrocytes and its metabolites after SAH causes vasoconstriction and neuronal damage, and correlates with delayed ischemic neurological deficits (DIND). While animal models have provided substantial and invaluable data in the research of aneurysmal SAH, the specific effects of subarachnoid blood on cerebral arteries remain greatly understudied. Here, we describe the changes in the genetic profile of human cerebral arteries exposed to free Hb for 48 h. We performed an exposure, followed by mRNA sequencing of the vessels. Compared to controls 54 genes were downregulated, and 53 genes were upregulated in human cerebral arteries after Hb exposure. Enrichment analysis identified the ferroptosis pathway as the most significantly affected. Further lipid peroxidation (LPO) assays and elevated gene expression support a ferroptosis pathway. Additionally, Hb exposure altered key signaling pathways essential for vascular stability (PI3K-Akt, MAPK), modified G-protein signaling mediated by , and suppressed key transcription factors such as and . Our results underscore the critical role of Hb in driving pathological responses in brain vessels. Furthermore, our dataset could be valuable for developing interventions after SAH and may help identify the underlying causes of vascular injury.
蛛网膜下腔出血（SAH）的特征是蛛网膜下腔存在血红蛋白（Hb），它会对脑血管产生显著影响，导致各种病理结果。SAH后红细胞释放的游离Hb及其代谢产物的毒性会引起血管收缩和神经元损伤，并与延迟性缺血性神经功能缺损（DIND）相关。虽然动物模型在动脉瘤性SAH的研究中提供了大量且宝贵的数据，但蛛网膜下腔血液对脑动脉的具体影响仍未得到充分研究。在此，我们描述了暴露于游离Hb 48小时的人脑动脉基因谱的变化。我们进行了一次暴露，随后对血管进行mRNA测序。与对照组相比，Hb暴露后人脑动脉中有54个基因下调，53个基因上调。富集分析确定铁死亡途径是受影响最显著的途径。进一步的脂质过氧化（LPO）测定和基因表达升高支持铁死亡途径。此外，Hb暴露改变了血管稳定性所必需的关键信号通路（PI3K-Akt、MAPK），改变了由其介导的G蛋白信号，并抑制了关键转录因子，如 和 。我们的结果强调了Hb在驱动脑血管病理反应中的关键作用。此外，我们的数据集对于开发SAH后的干预措施可能有价值，并可能有助于确定血管损伤的潜在原因。
