Engineering Therapeutics to Detoxify Hemoglobin, Heme, and Iron.

IF 12.8 1区 工程技术 Q1 ENGINEERING, BIOMEDICAL
Ivan S Pires, François Berthiaume, Andre F Palmer
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引用次数: 0

Abstract

Hemolysis (i.e., red blood cell lysis) can increase circulatory levels of cell-free hemoglobin (Hb) and its degradation by-products, namely heme (h) and iron (Fe). Under homeostasis, minor increases in these three hemolytic by-products (Hb/h/Fe) are rapidly scavenged and cleared by natural plasma proteins. Under certain pathophysiological conditions, scavenging systems become overwhelmed, leading to the accumulation of Hb/h/Fe in the circulation. Unfortunately, these species cause various side effects such as vasoconstriction, hypertension, and oxidative organ damage. Therefore, various therapeutics strategies are in development, ranging from supplementation with depleted plasma scavenger proteins to engineered biomimetic protein constructs capable of scavenging multiple hemolytic species. In this review, we briefly describe hemolysis and the characteristics of the major plasma-derived protein scavengers of Hb/h/Fe. Finally, we present novel engineering approaches designed to address the toxicity of these hemolytic by-products.

解毒血红蛋白、血红素和铁的工程疗法。
溶血(即红细胞裂解)可以增加无细胞血红蛋白(Hb)及其降解副产物,即血红素(h)和铁(Fe)的循环水平。在稳态下,这三种溶血副产物(Hb/h/Fe)的轻微增加会被天然血浆蛋白迅速清除。在某些病理生理条件下,清除系统不堪重负,导致循环中Hb/h/Fe的积累。不幸的是,这些物种会引起各种副作用,如血管收缩、高血压和氧化性器官损伤。因此,各种治疗策略正在开发中,从补充耗尽的血浆清除剂蛋白到能够清除多种溶血物种的工程仿生蛋白构建体。在这篇综述中,我们简要介绍了溶血和主要血浆来源的Hb/h/Fe蛋白清除剂的特性。最后,我们提出了新的工程方法,旨在解决这些溶血副产物的毒性。
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来源期刊
Annual Review of Biomedical Engineering
Annual Review of Biomedical Engineering 工程技术-工程:生物医学
CiteScore
18.80
自引率
0.00%
发文量
14
期刊介绍: Since 1999, the Annual Review of Biomedical Engineering has been capturing major advancements in the expansive realm of biomedical engineering. Encompassing biomechanics, biomaterials, computational genomics and proteomics, tissue engineering, biomonitoring, healthcare engineering, drug delivery, bioelectrical engineering, biochemical engineering, and biomedical imaging, the journal remains a vital resource. The current volume has transitioned from gated to open access through Annual Reviews' Subscribe to Open program, with all articles published under a CC BY license.
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