Nitrous oxide abuse leading to extreme homocysteine levels and thrombosis in young adults: a case series.

Background: Neurologic complications from recreational use of nitrous oxide (NO), which are attributed to vitamin B12 deficiency, have been well documented. With increasing dosages and frequency of NO use, an additional association with thromboembolisms is becoming apparent.

Objectives: To assess thrombotic complications of recreational NO use.

Ext1 heterozygosity causes a modest effect on postprandial lipid clearance in humans.

Elevated nonfasting TG-rich lipoprotein levels are a risk factor for CVD. To further evaluate the relevance of LDL-receptor (LDLr) pathway and heparan sulfate proteoglycans (HSPGs) in TG homeostasis, we analyzed fasting and postprandial TG levels in mice bearing combined heterozygous mutations in both Exostosin (Ext) 1 and Ldlr, in subjects with hereditary multiple exostosis (HME) due to a heterozygous loss-of-function mutation in EXT1 or EXT2 (N = 13), and in patients with heterozygous mutations in LDLR [familial hypercholesterolemia (FH)] and SNPs in major HSPG-related genes (n = 22). Mice bearing a homozygous mutation in hepatic Ext1 exhibited elevated plasma TGs similar to mice lacking other key enzymes involved in HSPG assembly.

Carriers of loss-of-function mutations in EXT display impaired pancreatic beta-cell reserve due to smaller pancreas volume.

Exotosin (EXT) proteins are involved in the chain elongation step of heparan sulfate (HS) biosynthesis, which is intricately involved in organ development. Loss of function mutations (LOF) in EXT1 and EXT2 result in hereditary exostoses (HME). Interestingly, HS plays a role in pancreas development and beta-cell function, and genetic variations in EXT2 are associated with an increased risk for type 2 diabetes mellitus.

SULF2 strongly prediposes to fasting and postprandial triglycerides in patients with obesity and type 2 diabetes mellitus.

Objective: Hepatic overexpression of sulfatase-2 (SULF2), a heparan sulfate remodeling enzyme, strongly contributes to high triglyceride (TG) levels in obese, type 2 diabetic (T2DM) db/db mice. Nevertheless, data in humans are lacking. Here, the association of human hepatic SULF2 expression and SULF2 gene variants with TG metabolism in patients with obesity and/or T2DM was investigated.

Rapid insulin-mediated increase in microvascular glycocalyx accessibility in skeletal muscle may contribute to insulin-mediated glucose disposal in rats.

It has been demonstrated that insulin-mediated recruitment of microvascular blood volume is associated with insulin sensitivity. We hypothesize that insulin rapidly stimulates penetration of red blood cells (RBC) and plasma into the glycocalyx and thereby promotes insulin-mediated glucose uptake by increasing intracapillary blood volume. Experiments were performed in rats; the role of the glycocalyx was assessed by enzymatic degradation using a bolus of hyaluronidase.

The metabolism of triglyceride-rich lipoproteins revisited: new players, new insight.

Peripheral lipoprotein lipase (LPL)-mediated lipolysis of triglycerides is the first step in chylomicron/VLDL clearance involving heparan sulfate proteoglycans (HSPGs) displayed at the cell surface of the capillaries in adipose tissue, heart and skeletal muscle. The newly generated chylomicron remnant particles are then cleared by the liver, whereas VLDL remnant particles are either further modified, through the action of hepatic lipase (HL) and cholesteryl ester transfer protein (CETP), into LDL particles or alternatively directly cleared by the liver. Two proteins, lipase maturation factor 1 (LMF1) and glycosylphosphatidylinositol-anchored high density lipoprotein binding protein 1 (GPIHBP1), have been recently identified and have revised our current understanding of LPL maturation and LPL-mediated lipolysis.

Endothelial glycocalyx as potential diagnostic and therapeutic target in cardiovascular disease.

Purpose Of Review: The endothelial glycocalyx has emerged as a potential orchestrator of vascular homeostasis. Under physiological conditions, the glycocalyx is an important contributor to the regulation of vascular permeability for macromolecules as well for the adhesion of circulating cells. In line, the potential role of the glycocalyx in maintaining the antiatherogenic properties of the vessel wall may have important clinical implications.

Partial recovery of the endothelial glycocalyx upon rosuvastatin therapy in patients with heterozygous familial hypercholesterolemia.

The endothelial glycocalyx has been shown to serve as a protective barrier between the flowing blood and the vessel wall in experimental models. The aim of this study was to evaluate whether hypercholesterolemia is associated with glycocalyx perturbation in humans, and if so, whether statin treatment can restore this. We measured systemic glycocalyx volume (V(G)) in 13 patients with heterozygous familial hypercholesterolemia (FH) after cessation of lipid-lowering therapy for a minimum of 4 weeks and 8 weeks after initiating rosuvastatin therapy.

Measuring endothelial glycocalyx dimensions in humans: a potential novel tool to monitor vascular vulnerability.

The endothelial glycocalyx is increasingly considered as an intravascular compartment that protects the vessel wall against pathogenic insults. The purpose of this study was to translate an established experimental method of estimating capillary glycocalyx dimension into a clinically useful tool and to assess its reproducibility in humans. We first evaluated by intravital microscopy the relation between the distance between the endothelium and erythrocytes, as a measure of glycocalyx thickness, and the transient widening of the erythrocyte column on glycocalyx compression by passing leukocytes in hamster cremaster muscle capillaries.

Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes.

Chronic hyperglycemia underlies microvascular complications in patients with type 1 diabetes. The mechanisms leading to these vascular complications are not fully understood. Recently, we observed that acute hyperglycemia results in endothelial glycocalyx damage.

Loss of endothelial glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo.

Hyperglycemia is associated with increased susceptibility to atherothrombotic stimuli. The glycocalyx, a layer of proteoglycans covering the endothelium, is involved in the protective capacity of the vessel wall. We therefore evaluated whether hyperglycemia affects the glycocalyx, thereby increasing vascular vulnerability.