Study: Animal Study: 12 papers
Peer-reviewed work on the endothelial glycocalyx, microvascular health and the ingredients in our formulas, newest first. Abstracts are indexed here and every paper links to the journal.
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Published paper
Early impairment of skeletal muscle endothelial glycocalyx barrier properties in diet-induced obesity in mice.
This mouse study examined whether the endothelial glycocalyx in skeletal muscle microvessels is damaged early in the course of diet-induced obesity. Using intravital measurement of glycocalyx barrier properties (accessibility of the glycocalyx to circulating tracers/red blood cells) in mice fed a high-fat diet, the authors found loss of glycocalyx barrier function before or alongside the development of overt metabolic disease. The findings suggest the glycocalyx is an early target of obesogenic diet rather than a late consequence of established obesity.
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Published paper
Rapid insulin-mediated increase in microvascular glycocalyx accessibility in skeletal muscle may contribute to insulin-mediated glucose disposal in rats.
In rats, systemic insulin infusion rapidly increased the accessible (perfused) volume of the endothelial glycocalyx in skeletal muscle microvessels, measured as increased distribution volume of a glycocalyx-permeable tracer. Enzymatic degradation of the glycocalyx with hyaluronidase blunted both this insulin-induced increase in glycocalyx accessibility and insulin-mediated glucose disposal. The authors conclude that insulin-driven changes in glycocalyx accessibility may contribute to how insulin promotes glucose uptake by muscle.
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Published paper
Long-term efficacy of liposomal nanocarriers of preassembled glycocalyx in restoring cerebral endothelial glycocalyx in sepsis
Researchers used a chronic cranial window and sidestream dark-field imaging (GlycoCheck analysis) to track cerebral microvascular density and perfused boundary region (PBR, an inverse index of glycocalyx thickness) in mice given LPS to model sepsis. LPS reduced vascular density and increased PBR within 3 hours; intravenous liposomal nanocarriers carrying preassembled glycocalyx (glycosylated syndecan-1 inserted into liposomes) blunted the PBR rise, with two doses giving longer-lasting benefit than one. Untreated animals recovered PBR spontaneously by 48 hours and vascular density by 72 hours.
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Published paper
Doxycycline protects against sepsis-induced endothelial glycocalyx shedding
In a rat model of sepsis induced by intraperitoneal E. coli lipopolysaccharide, pretreatment with oral doxycycline (an inhibitor of matrix metalloproteinases) largely preserved the endothelial glycocalyx in heart and lung capillaries, as shown by electron microscopy, lower serum syndecan-1, and lower perfused boundary region on mesenteric video capillaroscopy. Doxycycline-pretreated animals also had less vascular leakage, less perivascular edema, fewer transmigrating neutrophils, and better microvascular health scores. The authors attribute the effect to MMP inhibition, although MMP activity was not measured directly.
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Published paper
Sidestream dark field video microscopy demonstrates shelf-stable blood products preserve the endothelial glycocalyx in a canine hemorrhagic shock model
Six anesthetized dogs underwent induced hemorrhagic shock and were each resuscitated with five different fluid or blood-product strategies in a crossover design, with the endothelial glycocalyx assessed by sidestream dark field video microscopy (perfused boundary region, PBR). Crystalloid plus hydroxyethyl starch resuscitation was associated with increased PBR (indicating glycocalyx degradation), whereas chilled whole blood, plasma plus packed red cells, and shelf-stable products (freeze-dried plasma with a hemoglobin-based oxygen carrier, with or without lyophilized platelets) did not show significant PBR change from baseline.
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Published paper
Sidestream dark field imaging and biomarker evaluation reveal minimal significant changes to the microcirculation and glycocalyx in a canine hemorrhagic shock model
Eight anesthetized purpose-bred dogs underwent pressure-targeted hemorrhagic shock followed by fresh whole blood retransfusion, with sublingual sidestream dark field (GlycoCheck) imaging and plasma glycocalyx biomarkers measured at five time points. Despite marked drops in mean arterial pressure and cardiac output during shock, the perfused boundary region and microcirculatory variables did not change significantly, and only heparan sulfate showed a significant change (a decrease) over time.
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Published paper
Glycocalyx-targeted therapy ameliorates age-related arterial dysfunction
In mice, researchers reduced glycocalyx thickness by knocking down hyaluronan synthase 2 (Has2) and found this reproduced hallmarks of arterial aging: impaired endothelium-dependent dilation and increased aortic stiffness. Conversely, feeding old mice for 10 weeks with a glycocalyx-component supplement (Endocalyx, containing high-molecular-weight hyaluronan, glucosamine sulfate, fucoidan and superoxide dismutase) or with high-molecular-weight hyaluronan alone restored glycocalyx thickness and barrier function and improved endothelial function, aortic stiffness and blood pressure. Aortic wall composition (collagen, elastin) in supplemented old mice also resembled that of young mice.
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Published paper
Induced Trf2 deletion leads to aging vascular phenotype in mice associated with arterial telomere uncapping, senescence signaling, and oxidative stress
Researchers deleted the telomere-protecting protein Trf2 in adult mice to force telomere 'uncapping' without shortening telomeres, then measured artery and microvessel function. Trf2 deletion produced senescence signaling, oxidative stress, impaired nitric-oxide-dependent vasodilation, thinner endothelial glycocalyx, reduced microvascular perfusion, and modestly higher systolic blood pressure — a pattern resembling normal vascular aging.
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Published paper
Effect of acute hypernatremia induced by hypertonic saline administration on endothelial glycocalyx in rabbits.
In 20 rabbits, acute hypernatremia was induced with intravenous 10% NaCl and the sublingual and brain microcirculation were imaged with sidestream dark-field video microscopy before and 20 minutes after infusion. The perfused boundary region (PBR), an index of red blood cell penetration into the endothelial glycocalyx, increased slightly in the sublingual area, while blood syndecan-1 did not change. The authors interpret this as compression or charge alteration of the glycocalyx from transient hypervolemia rather than true shedding.
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Published paper
The Effect of Fluid Loading and Hypertonic Saline Solution on Cortical Cerebral Microcirculation and Glycocalyx Integrity.
In a rabbit craniotomy model, researchers compared one hour of liberal (30 mL/kg/h) versus restrictive (<2 mL/kg/h) balanced isotonic fluid administration, followed by a bolus of either 3.2% hypertonic saline or 0.9% saline. Cortical cerebral microcirculation was imaged with sidestream dark-field video microscopy, and glycocalyx integrity was assessed by the perfused boundary region (PBR) and serum syndecan-1. Liberal fluid loading was associated with poorer cortical vessel perfusion and signs of greater glycocalyx shedding, while hypertonic saline had no measurable effect on these parameters.
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Published paper
Advanced age results in a diminished endothelial glycocalyx
Researchers compared the endothelial glycocalyx in young and old mice (using intravital and electron microscopy) and in younger and older humans (using sublingual intravital microscopy with automated analysis). In both species, older subjects had a thinner, more penetrable glycocalyx along with reduced markers of microvascular perfusion. The findings suggest glycocalyx deterioration accompanies age-related microvascular dysfunction across mammalian species.
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Published paper
Perturbed mechanotransduction by endothelial surface glycocalyx modification greatly impairs the arteriogenic process
In mice, the glycocalyx component hyaluronan was reduced by continuous infusion of the hyaluronan synthase inhibitor 4-methylesculetin before surgical ligation of the femoral artery. Mice with a modified (thinner) endothelial glycocalyx showed markedly impaired recovery of blood flow and failed to enlarge collateral arteries. The authors conclude that an intact glycocalyx is needed for endothelial cells to sense altered shear stress and initiate arteriogenesis.
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