{"title":"Engineering Therapeutics to Detoxify Hemoglobin, Heme, and Iron.","authors":"Ivan S Pires, François Berthiaume, Andre F Palmer","doi":"10.1146/annurev-bioeng-081622-031203","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":50757,"journal":{"name":"Annual Review of Biomedical Engineering","volume":"25 ","pages":"1-21"},"PeriodicalIF":12.8000,"publicationDate":"2023-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Annual Review of Biomedical Engineering","FirstCategoryId":"5","ListUrlMain":"https://doi.org/10.1146/annurev-bioeng-081622-031203","RegionNum":1,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
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.
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.