heparitin-sulfate and Wounds-and-Injuries

Heparan sulfate is an integral component of the glycocalyx that provides an anticoagulant layer close to the endothelium. Hypoperfusion, inflammation, and sympathoadrenal activation following major trauma result in glycocalyx shedding and subsequent release of heparan sulfate into the bloodstream. The possible anticoagulant effect of this "autoheparinization" has been suggested as a potential driver of trauma-induced coagulopathy. We investigated whether thromboelastometry can be used to detect trauma-induced autoheparinization.. This study comprised three parts. First, in a retrospective clinical study of 264 major trauma patients, the clotting time (CT) in the intrinsic activation (INTEM) and intrinsic activation plus heparinase (HEPTEM) assays were evaluated upon emergency room admission. Second, in an in vivo experimental rat model of hemorrhagic-traumatic shock, the release of heparan sulfate was investigated with INTEM and HEPTEM analyses of whole blood. Third, in vitro spiking of whole blood from healthy volunteers was undertaken to assess the effects of clinically relevant quantities of heparan sulfate and heparin on CT in the INTEM and HEPTEM assays.. In the first part, severe injury and hemorrhagic shock was not associated with any increases in INTEM CT versus HEPTEM CT. Part 2 showed that an approximate threefold increase in heparan sulfate resulting from hemorrhagic traumatic shock in rats did not prolong INTEM CT, and no significant differences between INTEM CT and HEPTEM CT were observed. Third, spiking of whole blood with heparan sulfate had no impact on INTEM CT, whereas heparin elicited significant prolongation of INTEM CT.. Despite structural similarity between heparan sulfate and heparin, the amounts of heparan sulfate shed in response to trauma did not exert an anticoagulant effect that was measurable by the intrinsically activated CT in thromboelastometry. The extent to which heparan sulfate contributes to trauma-induced coagulopathy has yet to be elucidated.. Prognostic and Epidemiologic; Level III.

Topics: Animals; Blood Coagulation Disorders; Blood Coagulation Tests; Female; Glycocalyx; Heparin; Heparitin Sulfate; Humans; Male; Rats; Retrospective Studies; Shock, Hemorrhagic; Thrombelastography; Wounds and Injuries

One of the biggest challenges faced by healthcare providers is the treatment of chronic, non-healing wounds. This paper reports for the first time in the UK the results of five case studies in which a novel regenerating matrix-based therapy, CACIPLIQ20, was used. CACIPLIQ20 is a heparan sulphate mimetic designed to replace the destroyed heparan sulphate in the extracellular matrix of wound cells. All five patients in this case series had chronic, non-healing ulcers that had not improved with conventional care. Treatment included two applications of CACIPLIQ20 per week, for a maximum of 12 weeks. Three of the five wounds healed completely, and the remaining two showed significant improvements in size and quality. The treatment was well tolerated by the patients and also led to a significant reduction in pain. Moreover, CACIPLIQ20 treatment was found to be highly cost-effective when compared to conventional care, with the potential to save healthcare systems significant resources. Further studies are needed to build a strong evidence base on the use of this product, but these preliminary findings are certainly promising.

Topics: Adult; Aged; Aged, 80 and over; Amputation, Surgical; Bandages; Chronic Disease; Cost-Benefit Analysis; Extracellular Matrix; Female; Glucans; Heparitin Sulfate; Humans; Inflammation; Male; Middle Aged; Peripheral Vascular Diseases; Pressure Ulcer; Regeneration; Surgical Wound; Varicose Ulcer; Wounds and Injuries

Life-threatening cardiomyopathy is a severe, but common, complication associated with severe trauma or sepsis. Several signaling pathways involved in apoptosis and necroptosis are linked to trauma- or sepsis-associated cardiomyopathy. However, the underling causative factors are still debatable. Heparan sulfate (HS) fragments belong to the class of danger/damage-associated molecular patterns liberated from endothelial-bound proteoglycans by heparanase during tissue injury associated with trauma or sepsis. We hypothesized that HS induces apoptosis or necroptosis in murine cardiomyocytes. By using a novel Medical-

Topics: Algorithms; Animals; Apoptosis; Cardiomyopathies; Caspase 3; Cell Culture Techniques; Cells, Cultured; Cytochromes c; Heparitin Sulfate; Humans; Machine Learning; Mice; Myocytes, Cardiac; Necrosis; Receptor-Interacting Protein Serine-Threonine Kinases; Sepsis; Signal Transduction; Wounds and Injuries

Heparan sulfate (HS) is ubiquitous throughout the human body. The backbone of HS is composed of many types of sugars. HS serves as a docking site for a vast array of protein ligands. Recent evidence suggests a unique diversity in HS structure that alters protein binding and protein function. This diversity in HS structure has been overlooked till now. The goal of this study was to determine whether femoral artery wire injury modified HS structure. Femoral artery wire injury was performed in 16-week-old male C57BL6 mice. Transcript levels of a panel of enzymes that regulate HS fine structure, including N-deacetylase-N-sulfotransferases (Ndst) 1 and 2, exostoses (Ext) 1 and 2, C5 epimerase, and 2-O and 6-O sulfotransferases, were quantified with real-time quantitative polymerase chain reaction at 7 and 14 days post injury. All enzymes showed significant alterations in messenger RNA expression in response to injury. Ndst1, the most prevalent isoform, exhibited a 20-fold increase in response to injury. Injury induced significant alterations in fine structure specially increases in N-sulfated disaccharides at 14 days post injury. Vascular injury invokes transcriptional regulation of the enzymes that regulate HS structure, as well as changes in the pattern of HS chains in the vessel wall 14 days post injury. These findings may be important as the foundation of altered growth factor and chemokine binding in the process of vascular remodeling.

Topics: Animals; Chromatography, High Pressure Liquid; Computer Systems; Disaccharides; Femoral Artery; Heparitin Sulfate; Male; Mice; Mice, Inbred C57BL; Polymerase Chain Reaction; Protein Processing, Post-Translational; RNA, Messenger; Sulfotransferases; Transcription, Genetic; Wounds and Injuries

The activity of fibroblast growth factor 2 (FGF-2) is stringently controlled. Inactive in undisturbed tissues, it is activated during injury and is critical for tissue repair. We find that this control can be imposed by the soluble syndecan-1 ectodomain, a heparan sulfate proteoglycan shed from cell surfaces into wound fluids. The ectodomain potently inhibits heparin-mediated FGF-2 mitogenicity because of the poorly sulfated domains in its heparin sulfate chains. Degradation of these regions by platelet heparanase produces heparin-like heparin sulfate fragments that markedly activate FGF-2 mitogenicity and are found in wound fluids. These results establish a novel physiological control for FGF-2 and suggest new ways to modulate FGF activity.

Topics: Binding Sites; Exudates and Transudates; Fibrinolytic Agents; Fibroblast Growth Factor 2; Glucuronidase; Glycoside Hydrolases; Heparin; Heparitin Sulfate; Humans; Membrane Glycoproteins; Mitogens; Oligosaccharides; Protein Binding; Proteoglycans; Receptor Protein-Tyrosine Kinases; Receptor, Fibroblast Growth Factor, Type 1; Receptors, Fibroblast Growth Factor; Solubility; Syndecan-1; Syndecans; Wounds and Injuries

The aim of this study was to investigate whether heparan sulfate, as an adjunct to resuscitation following hemorrhagic shock: (1) improves gut absorptive capacity and if so, (2) whether the mechanism involved is alteration of whole blood viscosity (WBV). Rats were anesthetized, a laparotomy performed, and blood vessels cannulated. The conscious animals then underwent fixed pressure (40 mm Hg) hemorrhage, followed by resuscitation with lactated Ringer's solution. One group received 7 mg/kg heparan sulfate, and another received saline, during resuscitation. At 2 hours and 4 hours after the end of hemorrhage, the oral D-xylose absorption test was performed. Viscosity determinations were made in another set of rats since lactated Ringer's solution replacement during the D-xylose test may affect hematocrit and hence WBV. These rats were subjected to hemorrhage and resuscitation as above, along with additional sham hemorrhage and acute hemodilution control groups. The WBV was determined at corresponding times to the D-xylose test. Results show that xylose absorption is depressed after hemorrhage and resuscitation, and heparan sulfate restored it to normal. The WBV was reduced by heparan sulfate. Thus heparan sulfate, as an adjunct to resuscitation of hemorrhagic shock, restores gut absorptive capacity to normal, possibly by reducing WBV.

Topics: Animals; Blood Pressure; Blood Viscosity; Hematocrit; Heparitin Sulfate; Intestinal Absorption; Male; Rats; Rats, Sprague-Dawley; Resuscitation; Shock, Hemorrhagic; Wounds and Injuries; Xylose