期刊
NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE
卷 38, 期 -, 页码 -出版社
ELSEVIER
DOI: 10.1016/j.nano.2021.102449
关键词
Acute kidney injury; Thrombosis; Inflammation; Perfluorocarbon nanoparticles; Vessel damage
资金
- National Institutes of Health [DK102691, AR067491, HL073646, HL125353, HD087198, AI139072, DK125322]
- Veteran's Administration [I BX001792, 13F-RCS-002]
This study demonstrates that inhibition of thrombin-driven clotting and inflammatory signaling using locally-acting thrombin-targeted perfluorocarbon nanoparticles protects renal vasculature and modulates various inflammatory processes that cause renal ischemia reperfusion injury.
Acute kidney injury (AM) management remains mainly supportive as no specific therapeutic agents directed at singular signaling pathways have succeeded in clinical trials. Here, we report that inhibition of thrombin-driven clotting and inflammatory signaling with use of locally-acting thrombin-targeted perfluorocarbon nanoparticles (PFC NP) protects renal vasculature and broadly modulates diverse inflammatory processes that cause renal ischemia reperfusion injury. Each PFC NP was complexed with similar to 13,650 copies of the direct thrombin inhibitor, PPACK (proline-phenylalanine-arginine-chloromethyl-ketone). Mice treated after the onset of AM with PPACK PFC NP exhibited downregulated VCAM-1, ICAM-1, PGD2 prostanoid, M-CSF, IL-6, and mast cell infiltrates. Microvascular architecture. tubular basement membranes, and brush border components were better preserved. Non-reperfusion was reduced as indicated by reduced red blood cell trapping and non-heme iron. Kidney function and tubular necrosis improved at 24 hours versus the untreated control group, suggesting a benefit for dual inhibition of thrombosis and inflammation by PPACK PFC NP. (C) 2021 The Author(s). Published by Elsevier Inc.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据