一氧化氮
医学
伊诺斯
缺血
药理学
血管生成
缺氧(环境)
血管通透性
PI3K/AKT/mTOR通路
癌症研究
内科学
信号转导
一氧化氮合酶
细胞生物学
化学
生物
有机化学
氧气
作者
Papia Basuthakur,Arpita Roy,Soumya Ghosh,Vincy Vijay,Debiprasad Sinha,Mydhili Radhakrishnan,Arvind Kumar,Chitta Ranjan Patra,Sumana Chakravarty
出处
期刊:ACS applied bio materials
[American Chemical Society]
日期:2024-06-07
卷期号:7 (7): 4389-4405
标识
DOI:10.1021/acsabm.4c00252
摘要
Critical limb ischemia (CLI) refers to a severe condition resulting from gradual obstruction in the supply of blood, oxygen, and nutrients to the limbs. The most promising clinical solution to CLI is therapeutic angiogenesis. This study explored the potency of pro-angiogenic terbium hydroxide nanorods (THNR) for treatment of CLI, with a major focus on their impact on ischemia-induced maladaptive alterations in endothelial cells as well as on vascularization in ischemic limbs. This study demonstrated that, in hypoxia-exposed endothelial cells, THNR improve survival and promote proliferation, migration, restoration of nitric oxide production, and regulation of vascular permeability. Based on molecular studies, these attributes of THNR can be traced to the stimulation of PI3K/AKT/eNOS signaling pathways. Besides, Wnt/GSK-3β/β-catenin signaling pathways may also play a role in the therapeutic actions of THNR. Furthermore, in the murine model of CLI, THNR administration can integrally re-establish blood perfusion with concomitant reduction of muscle damage and inflammation. Additionally, improvement of locomotor activities and motor coordination in ischemic limbs in THNR treated mice is also evident. Overall, the study demonstrates that THNR have the potential to be developed as an efficacious and cost-effective alternative clinical therapy for CLI, using a nanomedicine approach.
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