Review: Contaminants in Heparin: Review of the Literature, Molecular Profiling, and Clinical Implications

Ramacciotti, Eduardo; Clark, Marin K.; Sadeghi, Nasir; Hoppensteadt, Debra; Thethi, Indermohan; Gomes, Marise; Fareed, Jawed

doi:10.1177/1076029610392214

Cited by 21 publications

(18 citation statements)

References 32 publications

(58 reference statements)

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“…By sulfation, it is also possible to add anticoagulant activity to HA (Chen et al, 1997). However, it should be mentioned that the misuse of chemically modified GAGs (other than Hep), as an alternative to overly used heparin, can lead to severe side reactions, as happened in 2007 and 2008, when heparin that was contaminated with oversulfated CS led to numerous deaths of patients (Liu et al, 2009;Ramacciotti et al, 2011).…”

Section: Application Of Glycosaminoglycans As Anticoagulantsmentioning

confidence: 99%

Medical application of glycosaminoglycans: a review

Köwitsch

Zhou

Groth

2017

J Tissue Eng Regen Med

179

145

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The characteristic molecular composition of the different glycosaminoglycans (GAGs) is related to their role as structural components and regulators of a multitude of functions of proteins, cells and tissues in the human body. Therefore, it is not surprising that GAGs are widely used as coating materials for implants, components of 3D-constructs such as tissue engineering scaffolds and hydrogels, but also as diagnostic devices such as biosensors and in controlled release applications. Beside a physisorption or encapsulation of GAGs, these applications often require their chemical modification to allow a stable covalent attachment on surfaces or cross-linking reactions with other molecules. Then, the preservation of the functionality of GAGs under maintenance of their biocompatibility is a challenging task and must be addressed in accordance with the designated field of application. Here, we will give a brief overview on structure and biological functions of GAGs, different methods of their activation and immobilization, the recent progress in GAG-related biomaterials development, as well as some examples of their application in the field of tissue engineering and regenerative medicine.

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Section: Application Of Glycosaminoglycans As Anticoagulantsmentioning

confidence: 99%

Medical application of glycosaminoglycans: a review

Köwitsch

Zhou

Groth

2017

J Tissue Eng Regen Med

179

145

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“…One particular important point is the “heparin contamination crisis”: this means that severe adverse events (even deaths) occurred when patients were treated with heparin that contained oversulfated CS. This has forced the Baxter Healthcare Corporation (as well as further companies) to recall many preparations of contaminated heparin 30 and significantly enhanced the interest in heparin analysis 31 …”

Section: The Architecture Of the Extracellular Matrixmentioning

confidence: 99%

New methods to study the composition and structure of the extracellular matrix in natural and bioengineered tissues

Schiller

Huster

2012

Biomatter

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The extracellular matrix (ECM) comprises a gel of numerous biopolymers that occurs in a multitude of biological tissues. The ECM provides the basic support and mechanical strength of skeletal tissue and is responsible for shape retention. At the same time, the ECM is responsible for the viscoelastic properties and the elasticity of soft tissues. As expected, there are several important diseases that affect and degenerate the ECM with severe consequences for its properties. Bioengineering is a promising approach to support the regenerative capacity of the body. Unfortunately, the biomechanical properties of bioengineered ECM often only poorly meet the standards of their native counterparts. Many bioengineered tissues are characterized by an increased glycosaminoglycan (GAG) but decreased collagen content. This leads to an enhanced water content that strongly alters the viscoelastic and thus the biomechanical properties. Therefore, compositional analysis is important to estimate the tissue quality. We will show that nuclear magnetic resonance (NMR) spectroscopy and soft-ionization mass spectrometry (MS) represent useful techniques for ECM research both in natural and bioengineered tissues. Both methods are strongly complimentary: while MS techniques such as matrix-assisted laser desorption and ionization (MALDI) are excellent and very sensitive analytical tools to determine the collagen and the GAG contents of tissues, NMR spectroscopy provides insight into the molecular architecture of the ECM, its dynamics and other important parameters such as the water content of the tissue as well as the diffusion of molecules within the ECM.

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“…Heparin is a sulfated glycosaminoglycan, which is widely applied as an injectable anticoagulant (17,18). Although used principally in medicine for anticoagulation, other biological and physiological roles of heparin, and its underlying mechanisms remain to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

Heparin inhibits the inflammation and proliferation of human rheumatoid arthritis fibroblast-like synoviocytes through the NF-κB pathway

Zhang

Wang

2016

Molecular Medicine Reports

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Abstract. Fibroblast-like synoviocytes (FLSs) of rheumatoid arthritis (RA) lead to cartilage destruction, and the activation of NF-κB is important in the proliferation of FLSs. Heparin is a glycosaminoglycan, which is widely used as an anticoagulant. In the present study, the effect of heparin on the tumor necrosis factor (TNF)-α induced proliferation of FLSs was investigated. Western blot and polymerase chain reaction analyses were used to assess the expression levels of cytokines. The results revealed that TNF-α induced the expression of interleukin (IL)-6, IL-8, TNF-α and cyclin D1. Heparin inhibited the growth rate of the FLSs induced by TNF-α. Heparin also decreased the TNF-α-induced mRNA and protein expression levels of IL-6, IL-8, TNF-α and cyclin D1 in a dose-dependent manner. Immunofluorescence analysis showed that the expression of cytoplasmic TNF-α was significantly reduced by heparin treatment. Furthermore, the levels of p65 and inhibitor of nuclear factor (NF)-κB phosphorylation were inhibited by heparin treatment, suggesting that heparin induced the inhibition of NF-κB. In conclusion, the results of the present study revealed that heparin inhibited the TNF-α-induced proliferation, cytokine production, expression of cyclin D1 and activation of NF-κB signaling in FLSs, indicating the therapeutic potential of heparin in the treatment of RA.

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Review: Contaminants in Heparin: Review of the Literature, Molecular Profiling, and Clinical Implications

Abstract: These results suggest that heparin contaminants represent a heterogeneous group of oversulfated glycosaminoglycans (OSGAGs) which may mediate multiple pathophysiologic responses.

Cited by 21 publications

References 32 publications

Medical application of glycosaminoglycans: a review

Medical application of glycosaminoglycans: a review

New methods to study the composition and structure of the extracellular matrix in natural and bioengineered tissues

Heparin inhibits the inflammation and proliferation of human rheumatoid arthritis fibroblast-like synoviocytes through the NF-κB pathway

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