Encapsulation of hemoglobin inside liposomes surface conjugated with poly(ethylene glycol) attenuates their reactions with gaseous ligands and regulates nitric oxide dependent vasodilation.
Encapsulation of hemoglobin inside liposomes surface conjugated with poly(ethylene glycol) attenuates their reactions with gaseous ligands and regulates nitric oxide dependent vasodilation.
复制标题
将血红蛋白封装在与聚乙二醇缀合的脂质体表面内，可减弱其与气体配体的反应，并调节一氧化氮依赖性血管舒张。
DOI：
10.1002/btpr.1532
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发表时间：
2012
影响因子：
2.9
通讯作者：
Honavar,Jaideep
中科院分区：
文献类型：
--
作者：
Rameez,Shahid;Guzman,Nicole;Banerjee,Uddyalok;Fontes,Jorge;Paulaitis,MichaelE;Palmer,AndreF;Patel,RakeshP;Honavar,Jaideep
基于脱细胞血红蛋白(HB)的氧气载体(HBOCs)正被研究为用于输血医学的红细胞(RBC)替代品。然而，商业脱细胞HBOCs会引起血管收缩和全身性高血压，这阻碍了它们的临床应用。在这项研究中，假设将Hb包裹在脂质体的水核中，可以调节NO的双氧合和O2的释放，从而调节其血管活性。为了验证这一假设，以人和牛的血红蛋白为原料制备了聚乙二醇脂质体包裹的血红蛋白分散体(PEGLEHS)。在这项研究中，我们用停流紫外可见光谱测量了游离HB和PEGLEH分散体的O2解离、CO结合和NO双氧合的速率常数，同时用内源性和外源性NO评估了大鼠主动脉环条的血管活性。结果表明，与无细胞HBS相比，聚乙二醇LEH分散体具有较低的O2释放量和无二氧速率常数。然而，自由HB和聚乙二醇LEH分散体之间的CO缔合速率常数没有差异。此外，还观察到囊泡内包裹Hb可阻止Hb对NO介导的血管扩张的依赖抑制。此外，HB和PEGLEH分散体的血管收缩效应的大小与它们各自的NO双氧合率和O2释放率有关。总体而言，本研究强调了Hb胶囊在调节气态配体结合/释放动力学和Hb的血管活性中所起的关键作用。©2012美国化学工程师学会生物技术。节目，2012年
Acellular hemoglobin (Hb)‐based O2carriers (HBOCs) are being investigated as red blood cell (RBC) substitutes for use in transfusion medicine. However, commercial acellular HBOCs elicit both vasoconstriction and systemic hypertension which hampers their clinical use. In this study, it is hypothesized that encapsulation of Hb inside the aqueous core of liposomes should regulate the rates of NO dioxygenation and O2release, which should in turn regulate its vasoactivity. To test this hypothesis, poly(ethylene glycol) (PEG) conjugated liposome‐encapsulated Hb (PEG‐LEHs) dispersions were prepared using human and bovine Hb. In this study, the rate constants for O2dissociation, CO association, and NO dioxygenation were measured for free Hb and PEG‐LEH dispersions using stopped‐flow UV–visible spectroscopy, while vasoactivity was assessed in rat aortic ring strips using both endogenous and exogenous sources of NO. It was observed that PEG‐LEH dispersions had lower O2release and NO dioxygenation rate constants compared with acellular Hbs. However, no difference was observed in the CO association rate constants between free Hb and PEG‐LEH dispersions. Furthermore, it was observed that Hb encapsulation inside vesicles prevented Hb dependent inhibition of NO‐mediated vasodilation. In addition, the magnitude of the vasoconstrictive effects of Hb and PEG‐LEH dispersions correlated with their respective rates of NO dioxygenation and O2release. Overall, this study emphasizes the pivotal role Hb encapsulation plays in regulating gaseous ligand binding/release kinetics and the vasoactivity of Hb. © 2012 American Institute of Chemical Engineers Biotechnol. Prog., 2012