Development of a Glycosaminoglycan Derived, Selectin Targeting Anti-Adhesive Coating to Treat Endothelial Cell Dysfunction

Wodicka, James R; Chambers, Andrea M.; Sangha, Gurneet S.; Goergen, Craig J.; Panitch, Alyssa

doi:10.3390/ph10020036

Cited by 20 publications

(27 citation statements)

References 58 publications

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“…A novel therapy (EC‐SEAL) to reduce deep vein thrombosis formation is in the development phase. The drug is composed of a synthetic GAG, DS, and multiple selectin binding sites 178 . EC‐SEAL utilizes its selectin binding sites to bind to activated or inflamed endothelium characterized by an increased expression of selectins on the luminal cell surface.…”

Section: Therapeutic Interventions To Preserve or Restore The Endothementioning

confidence: 99%

“…Binding by EC‐SEAL could restore the protective covering over platelet adhesion molecules and limit thrombus generation. In a mouse model of deep vein thrombosis, IV administration of EC‐SEAL reduced thrombus formation as assessed by vessel ultrasonography 178 …”

Section: Therapeutic Interventions To Preserve or Restore The Endothementioning

confidence: 99%

“…The drug is composed of a synthetic GAG, DS, and multiple selectin binding sites. 178 EC-SEAL utilizes its selectin binding sites to bind to activated or inflamed endothelium characterized by an increased expression of selectins on the luminal cell surface. Binding by EC-SEAL could restore the protective covering over platelet adhesion molecules and limit thrombus generation.…”

Section: Therapeutic Interventions To Preserve or Restore The Endothementioning

confidence: 99%

“…In a mouse model of deep vein thrombosis, IV administration of EC-SEAL reduced thrombus formation as assessed by vessel ultrasonography. 178 The use of heparin to reduce EG shedding has been investigated.…”

Section: Therapeutic Interventions To Preserve or Restore The Endothementioning

confidence: 99%

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The endothelial glycocalyx: Structure and function in health and critical illness

Gaudette

Hughes

Boller

2020

J Vet Emergen Crit Care

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Objective To conduct a narrative review of the current literature in reference to the structure and function of the endothelial glycocalyx (EG) and its contribution to the pathophysiology of conditions relevant to the veterinary emergency and critical care clinician. Novel therapies for restoring or preserving the EG will also be discussed. Data Sources Online databases (PubMed, CAB abstracts, Scopus) were searched between January 1st 2017 and May 1st 2017 for English language articles without publication date restriction. Keywords included EG, endothelial surface layer, degradation, syndecan‐1, heparan sulfate, critical illness, sepsis, trauma, and therapeutics. Data Synthesis The EG is a complex and important structure located on the luminal surface of all blood vessels throughout the body. It plays an important role in normal vascular homeostasis including control of fluid exchange across the vascular barrier. Loss or degradation of the EG has an impact on inflammation, coagulation, and vascular permeability and tone. These changes are essential components in the pathophysiology of many conditions including sepsis and trauma. A substantial body of experimental animal and human clinical research over the last decade has demonstrated increased circulating concentrations of EG degradation products in these conditions. However, veterinary‐specific research into the EG and critical illness is currently lacking. The utility of EG degradation products as diagnostic and prognostic tools continues to be investigated and new therapies to preserve or improve EG structure and function are under development. Conclusions The recognition of the presence of the EG has changed our understanding of transvascular fluid flux and the pathophysiology of many conditions of critical illness. The EG is an exciting target for novel therapeutics to improve morbidity and mortality in conditions such as sepsis and trauma.

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Section: Therapeutic Interventions To Preserve or Restore The Endothementioning

confidence: 99%

Section: Therapeutic Interventions To Preserve or Restore The Endothementioning

confidence: 99%

Section: Therapeutic Interventions To Preserve or Restore The Endothementioning

confidence: 99%

Section: Therapeutic Interventions To Preserve or Restore The Endothementioning

confidence: 99%

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The endothelial glycocalyx: Structure and function in health and critical illness

Gaudette

Hughes

Boller

2020

J Vet Emergen Crit Care

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“…The abdominal cavity was exposed via laparotomy, and the left kidney and renal vein were isolated. In the stenosed group, a 30-gauge needle was aligned parallel to the left renal vein and a silk 6-0 suture was tied around both the needle and the vein as done previously [14]. The needle was then removed to create a stenosis.…”

Section: Animal Studymentioning

confidence: 99%

Toward Automation of the Supine Pressor Test for Preeclampsia

Qureshi

Anderson

et al. 2019

Journal of Engineering and Science in Medical Diagnostics and Therapy

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Preeclampsia leads to increased risk of morbidity and mortality for both mother and fetus. Most previous studies have largely neglected mechanical compression of the left renal vein by the gravid uterus as a potential mechanism. In this study, we first used a murine model to investigate the pathophysiology of left renal vein constriction. The results indicate that prolonged renal vein stenosis after 14 days can cause renal necrosis and an increase in blood pressure (BP) of roughly 30 mmHg. The second part of this study aimed to automate a diagnostic tool, known as the supine pressor test (SPT), to enable pregnant women to assess their preeclampsia development risk. A positive SPT has been previously defined as an increase of at least 20 mmHg in diastolic BP when switching between left lateral recumbent and supine positions. The results from this study established a baseline BP increase between the two body positions in nonpregnant women and demonstrated the feasibility of an autonomous SPT in pregnant women. Our results demonstrate that there is a baseline increase in BP of roughly 10-14 mmHg and that pregnant women can autonomously perform the SPT. Overall, this work in both rodents and humans suggests that (1) stenosis of the left renal vein in mice leads to elevation in BP and acute renal failure, (2) nonpregnant women experience a baseline increase in BP when they shift from left lateral recumbent to supine position, and (3) the SPT can be automated and used autonomously.

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Photocurable extracellular matrix sealant for cessation of venous hemorrhage

Schepers,

Martindale,

Berman

et al. 2024

J Biomed Mater Res

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Hemorrhage is the second leading cause of death in patients under 46 years of age in the United States. Cessation of hemorrhage prevents hemorrhagic shock and tissue hypoxia. Controlling the bleed via direct pressure or tourniquet is often the first line of defense, but long‐term care requires staples, hemostatic agents, or sealants that seal the vessel and restore blood flow. Here, we compare a new photocurable extracellular matrix sealant (pcECM) with low, medium, and high crosslink density formulations to a commercially available fibrin‐based sealant, TISSEEL®. pcECM has potential uses in surgical and remote settings due to room temperature storage conditions and fast preparation time. Here, we determine if pcECM sealant can stop venous hemorrhage in a murine model, adhere to the wound site in vivo throughout the wound‐healing process, and has the mechanical properties necessary for stopping hemorrhage. Adjusting pcECM crosslinking density significantly affected viscosity, swelling, burst strength, tensile strength, and elasticity of the sealant. 3‐Dimensional ultrasound volume segmentations showed pcECM degrades to 17 ± 8% of its initial implant volume by day 28. Initially, local hemodynamic changes were observed, but returned close to baseline levels by day 28. Acute inflammation was observed near the puncture site in pcECM implanted mice, and we observed inflammatory markers at the 14‐day explant for both sealants. pcECM and fibrin sealant successfully sealed the vessel in all cases, and consistently degraded over 14–28 days. pcECM is a durable sealant with tunable mechanical properties and possible uses in hemorrhage control and other surgical procedures.

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Development of a Glycosaminoglycan Derived, Selectin Targeting Anti-Adhesive Coating to Treat Endothelial Cell Dysfunction

Cited by 20 publications

References 58 publications

The endothelial glycocalyx: Structure and function in health and critical illness

The endothelial glycocalyx: Structure and function in health and critical illness

Toward Automation of the Supine Pressor Test for Preeclampsia

Photocurable extracellular matrix sealant for cessation of venous hemorrhage

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