谷甾醇血症患者的红细胞表现为膜脂组成和分布受损,可变形性降低

Anne-Sophie Cloos, M. Rab, P. van der Smissen, B. V. van Oirschot, E. Mignolet, J. B. van der Net, A. Koster, Kelly Kleinen, Y. Larondelle, Romano Terrasi, G. Muccioli, R. van Wijk, D. Tyteca
{"title":"谷甾醇血症患者的红细胞表现为膜脂组成和分布受损,可变形性降低","authors":"Anne-Sophie Cloos, M. Rab, P. van der Smissen, B. V. van Oirschot, E. Mignolet, J. B. van der Net, A. Koster, Kelly Kleinen, Y. Larondelle, Romano Terrasi, G. Muccioli, R. van Wijk, D. Tyteca","doi":"10.3389/frhem.2023.1055086","DOIUrl":null,"url":null,"abstract":"Sitosterolemia is a metabolic disorder leading to excessive accumulation of phytosterols. Hemolytic stomatocytosis and macrothrombocytopenia are part of the clinical picture. However, the impact of phytosterols on red blood cell (RBC) deformability, membrane lipid composition and distribution and the efficiency of the reference treatment, Ezetimibe, are largely unknown. This study addresses these issues using RBCs from three patients with sitosterolemia and healthy RBCs exposed to β-sitosterol. Patients presented an increased proportion of stomatocytes, decreased RBC deformability and increased RBC hydration and osmotic fragility compared to healthy donors. At the membrane level, patient RBCs showed (i) very high content in β-sitosterols, (ii) increased proportions of saturated fatty acids and polyunsaturated fatty acid species with long and unsaturated carbon chains, and (iii) decreased content in phosphatidylethanolamine species. These lipid changes were accompanied by an almost complete abrogation of cholesterol-enriched domains, which could result from: (i) the reduced phosphatidylethanolamine content which positively correlated with domain abundance; and (ii) the fatty acid modifications and increased phytosterol content, both compatible with higher membrane stiffness. The role of β-sitosterol was supported by comparable changes in RBC morphology and cholesterol-enriched domains upon β-sitosterol integration at the healthy RBC membrane. Finally, Ezetimibe treatment combined with a sterol restricted diet lowered phytosterols and improved anemia and RBC deformability and hydration. However, this treatment had no or limited effect on RBC morphology and cholesterol-enriched domain abundance. This study reveals for the first time that phytosterols affect RBC membrane lipid composition and distribution but also RBC morphology, hydration, deformability and fragility.","PeriodicalId":101407,"journal":{"name":"Frontiers in hematology","volume":"57 1","pages":"0"},"PeriodicalIF":0.0000,"publicationDate":"2023-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Red blood cells from patients with sitosterolemia exhibit impaired membrane lipid composition and distribution and decreased deformability\",\"authors\":\"Anne-Sophie Cloos, M. Rab, P. van der Smissen, B. V. van Oirschot, E. Mignolet, J. B. van der Net, A. Koster, Kelly Kleinen, Y. Larondelle, Romano Terrasi, G. Muccioli, R. van Wijk, D. Tyteca\",\"doi\":\"10.3389/frhem.2023.1055086\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Sitosterolemia is a metabolic disorder leading to excessive accumulation of phytosterols. Hemolytic stomatocytosis and macrothrombocytopenia are part of the clinical picture. However, the impact of phytosterols on red blood cell (RBC) deformability, membrane lipid composition and distribution and the efficiency of the reference treatment, Ezetimibe, are largely unknown. This study addresses these issues using RBCs from three patients with sitosterolemia and healthy RBCs exposed to β-sitosterol. Patients presented an increased proportion of stomatocytes, decreased RBC deformability and increased RBC hydration and osmotic fragility compared to healthy donors. At the membrane level, patient RBCs showed (i) very high content in β-sitosterols, (ii) increased proportions of saturated fatty acids and polyunsaturated fatty acid species with long and unsaturated carbon chains, and (iii) decreased content in phosphatidylethanolamine species. These lipid changes were accompanied by an almost complete abrogation of cholesterol-enriched domains, which could result from: (i) the reduced phosphatidylethanolamine content which positively correlated with domain abundance; and (ii) the fatty acid modifications and increased phytosterol content, both compatible with higher membrane stiffness. The role of β-sitosterol was supported by comparable changes in RBC morphology and cholesterol-enriched domains upon β-sitosterol integration at the healthy RBC membrane. Finally, Ezetimibe treatment combined with a sterol restricted diet lowered phytosterols and improved anemia and RBC deformability and hydration. However, this treatment had no or limited effect on RBC morphology and cholesterol-enriched domain abundance. This study reveals for the first time that phytosterols affect RBC membrane lipid composition and distribution but also RBC morphology, hydration, deformability and fragility.\",\"PeriodicalId\":101407,\"journal\":{\"name\":\"Frontiers in hematology\",\"volume\":\"57 1\",\"pages\":\"0\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2023-03-07\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in hematology\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.3389/frhem.2023.1055086\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in hematology","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.3389/frhem.2023.1055086","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0

摘要

谷甾醇血症是一种导致植物甾醇过度积累的代谢紊乱。溶血性口细胞增多症和巨血小板减少症是临床表现的一部分。然而,植物甾醇对红细胞(RBC)可变形性、膜脂组成和分布以及依折替米贝(Ezetimibe)对照治疗的效率的影响在很大程度上是未知的。本研究利用三名谷甾醇血症患者的红细胞和暴露于β-谷甾醇的健康红细胞来解决这些问题。与健康供者相比,患者表现为气孔细胞比例增加,红细胞变形能力降低,红细胞水合性和渗透脆弱性增加。在膜水平,患者红细胞显示(i) β-谷甾醇含量非常高,(ii)具有长碳链和不饱和碳链的饱和脂肪酸和多不饱和脂肪酸种类的比例增加,(iii)磷脂酰乙醇胺种类的含量降低。这些脂质变化伴随着胆固醇富集结构域的几乎完全消失,这可能是由于:(1)与结构域丰度正相关的磷脂酰乙醇胺含量减少;脂肪酸修饰和植物甾醇含量增加,两者都与更高的膜刚度相适应。β-谷甾醇在健康红细胞膜上整合后,红细胞形态和胆固醇富集结构域的变化支持了β-谷甾醇的作用。最后,依折麦比联合限制固醇饮食降低了植物固醇,改善了贫血、红细胞变形能力和水合作用。然而,这种治疗对红细胞形态和胆固醇富集结构域丰度没有或有限的影响。本研究首次揭示了植物甾醇影响红细胞膜脂的组成和分布,同时也影响红细胞形态、水合作用、可变形性和易碎性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Red blood cells from patients with sitosterolemia exhibit impaired membrane lipid composition and distribution and decreased deformability
Sitosterolemia is a metabolic disorder leading to excessive accumulation of phytosterols. Hemolytic stomatocytosis and macrothrombocytopenia are part of the clinical picture. However, the impact of phytosterols on red blood cell (RBC) deformability, membrane lipid composition and distribution and the efficiency of the reference treatment, Ezetimibe, are largely unknown. This study addresses these issues using RBCs from three patients with sitosterolemia and healthy RBCs exposed to β-sitosterol. Patients presented an increased proportion of stomatocytes, decreased RBC deformability and increased RBC hydration and osmotic fragility compared to healthy donors. At the membrane level, patient RBCs showed (i) very high content in β-sitosterols, (ii) increased proportions of saturated fatty acids and polyunsaturated fatty acid species with long and unsaturated carbon chains, and (iii) decreased content in phosphatidylethanolamine species. These lipid changes were accompanied by an almost complete abrogation of cholesterol-enriched domains, which could result from: (i) the reduced phosphatidylethanolamine content which positively correlated with domain abundance; and (ii) the fatty acid modifications and increased phytosterol content, both compatible with higher membrane stiffness. The role of β-sitosterol was supported by comparable changes in RBC morphology and cholesterol-enriched domains upon β-sitosterol integration at the healthy RBC membrane. Finally, Ezetimibe treatment combined with a sterol restricted diet lowered phytosterols and improved anemia and RBC deformability and hydration. However, this treatment had no or limited effect on RBC morphology and cholesterol-enriched domain abundance. This study reveals for the first time that phytosterols affect RBC membrane lipid composition and distribution but also RBC morphology, hydration, deformability and fragility.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信