Background: Increased vascular permeability is a characteristic feature of sepsis which, in the past, has been ascribed exclusively to a malfunction of endothelial cells. However, recently it has become evident that the endothelial glycocalyx is of considerable importance concerning various aspects of vascular physiology, e.g. the vascular barrier and inflammation. Heparan sulfate, one of its essential components is characteristically traceable in blood, in case the endothelial glycocalyx is damaged or destroyed.
Methods: In 15 pigs we investigated whether the administration of endotoxin from gram-negative bacteria (Escherichia coli) results in increased serum levels of heparan sulfate, signalizing a shedding of the glycocalyx. In addition, markers of inflammation (white blood cell count, platelet count, tumour necrosis factor-α and interleukin-6) were evaluated over an observation period of 6 hours.
Results: Serum heparan sulfate concentrations significantly increased over time in the endotoxin group and were significantly elevated in comparison to the control group 6 hours after administration of endotoxin (p<0.001). In the endotoxin group all markers of inflammation significantly changed during the time course.
Conclusions: The administration of bacterial endotoxin induced a significant rise in degradation products of the endothelial glycocalyx.
Download full-text PDF |
Source |
---|---|
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3351938 | PMC |
http://dx.doi.org/10.1186/2047-783x-14-12-526 | DOI Listing |
Vaccines (Basel)
January 2025
Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Background: Noroviruses, which cause epidemic acute gastroenteritis, and parasites, which lead to malaria, are two infectious pathogens that pose threats to public health. The protruding (P) domain of norovirus VP1 and the αTSR domain of the circumsporozoite protein (CSP) of sporozoite are the glycan receptor-binding domains of the two pathogens for host cell attachment, making them excellent targets for vaccine development. Modified norovirus P domains self-assemble into a 24-meric octahedral P nanoparticle (P NP).
View Article and Find Full Text PDFShock
January 2025
The University of Alabama, Birmingham, Department of Surgery and Center for Injury Science, Division of Trauma and Acute Care Surgery, Birmingham, AL.
Introduction: Trauma and hemorrhagic shock (T/HS) are associated with multiple organ injury. Antithrombin (AT) has anti-inflammatory and organ protective activity through its interaction with endothelial heparan sulfate containing a 3-O-sulfate modification. Our objective was to examine the effects of T/HS on 3-O-sulfated (3-OS) heparan sulfate expression and determine whether AT-heparan sulfate interactions are necessary for its anti-inflammatory properties.
View Article and Find Full Text PDFFront Cell Dev Biol
January 2025
Department of Medical Biotechnologies, University of Siena, Siena, Italy.
By virtue of their ability to bind different growth factors, morphogens and extracellular matrix proteins, heparan sulfate proteoglycans (HSPGs) play a determinant role in cancer cell differentiation and migration. Despite a strong conceptual basis and promising preclinical results, clinical trials have failed to demonstrate any significant advantage of administering heparin to oncology patients. We exploited our anti-heparan sulfate branched peptide NT4 to test the opposite approach, namely, targeting HSPGs to interfere with their functions, instead of using heparin as a soluble competitor in human cell lines from pancreas adenocarcinoma, colon adenocarcinoma, rhabdomyosarcoma and two different breast cancers.
View Article and Find Full Text PDFJ Med Chem
January 2025
Department of Chemistry, Wayne State University, Detroit, Michigan 48202, United States.
Alzheimer's disease (AD) is the most common form of dementia, marked by progressive brain degeneration and cognitive decline. A major pathological feature of AD is the accumulation of hyperphosphorylated tau (p-tau) in the form of neurofibrillary tangles (NFTs), which leads to neuronal death and neurodegeneration. P-tau also induces endoplasmic reticulum (ER) stress and activates the unfolded protein response, causing inflammation and apoptosis.
View Article and Find Full Text PDFHypertension
January 2025
Division of Obstetrics and Gynecology, Institute of Clinical Sciences Lund, Lund University, Sweden. (C.E., F.P., L.E., S.R.H.).
Background: Preeclampsia is a hypertensive pregnancy disorder marked by endothelial damage. Healthy endothelium is covered by a protective glycocalyx layer, which, when degraded, releases detectable products into the blood. Sphingosine-1-phosphate (S1P) is a cardiovascular biomarker involved in glycocalyx preservation, linked to placentation and preeclampsia development.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!