Arterial heparan sulfate is negatively associated with hyperglycemia and atherosclerosis in diabetic monkeys

BACKGROUND: Arterial proteoglycans are implicated in the pathogenesis of atherosclerosis by their ability to trap plasma lipoproteins in the arterial wall and by their influence on cellular migration, adhesion and proliferation. In addition, data have suggested an anti-atherogenic role for heparan sulfate proteoglycans and a pro-atherogenic role for dermatan sulfate proteoglycans. Using a non-human primate model for human diabetes, studies examined diabetes-induced changes in arterial proteoglycans that may increase susceptibility to atherosclerosis. METHODS: Control (n = 7) and streptozotocin-induced diabetic (n = 8) cynomolgous monkeys were assessed for hyperglycemia by measurement of plasma glycated hemoglobin (GHb). Thoracic aortas obtained at necropsy, were extracted with 4 M guanidine HCL and proteoglycans were measured as hexuronic acid. Atherosclerosis was measured by enzymatic analysis of extracted tissue cholesterol. Glycosaminoglycan chains of arterial proteoglycans were released with papain, separated by agarose electrophoresis and analysed by scanning densitometry. RESULTS: Tissue cholesterol was positively associated with hexuronic acid content in diabetic arteries (r = .82, p < .025) but not in control arteries. Glycosaminoglycan chain analysis demonstrated that dermatan sulfate was associated with increased tissue cholesterol in both control (r = .8, p < 0.05) and diabetic (r = .8, p < .025) arteries, whereas a negative relationship was observed between heparan sulfate and tissue cholesterol in diabetic arteries only (r = -.7, p < .05). GHb, which was significantly higher in diabetic animals (8.2 ± 0.9 vs 3.8 ± 0.2%, p < .0005) was negatively associated with heparan sulfate in diabetic arteries (r = -.7, p < .05). CONCLUSIONS: These data implicate hyperglycemia induced modifications in arterial proteoglycans that may promote atherosclerosis

Serum Xylosyltransferase Activity in Diabetic Patients as a Possible Marker of Reduced Proteoglycan Biosynthesis

OBJECTIVE—Proteoglycan metabolism is altered in diabetic patients. The xylosyltransferases (XTs) are the initial and rate-limiting enzymes in the biosynthesis of the glycosaminoglycan chains in proteoglycans. Here, we analyzed whether the changed proteoglycan metabolism leads to altered serum XT levels in diabetic patients

Dyson-Schwinger Equations: Density, Temperature and Continuum Strong QCD

Continuum strong QCD is the application of models and continuum quantum field theory to the study of phenomena in hadronic physics, which includes; e.g., the spectrum of QCD bound states and their interactions; and the transition to, and properties of, a quark gluon plasma. We provide a contemporary perspective, couched primarily in terms of the Dyson-Schwinger equations but also making comparisons with other approaches and models. Our discourse provides a practitioners' guide to features of the Dyson-Schwinger equations [such as confinement and dynamical chiral symmetry breaking] and canvasses phenomenological applications to light meson and baryon properties in cold, sparse QCD. These provide the foundation for an extension to hot, dense QCD, which is probed via the introduction of the intensive thermodynamic variables: chemical potential and temperature. We describe order parameters whose evolution signals deconfinement and chiral symmetry restoration, and chronicle their use in demarcating the quark gluon plasma phase boundary and characterising the plasma's properties. Hadron traits change in an equilibrated plasma. We exemplify this and discuss putative signals of the effects. Finally, since plasma formation is not an equilibrium process, we discuss recent developments in kinetic theory and its application to describing the evolution from a relativistic heavy ion collision to an equilibrated quark gluon plasma.Comment: 103 Pages, LaTeX, epsfig. To appear in Progress in Particle and Nuclear Physics, Vol. 4

The endothelial glycocalyx: composition, functions, and visualization

This review aims at presenting state-of-the-art knowledge on the composition and functions of the endothelial glycocalyx. The endothelial glycocalyx is a network of membrane-bound proteoglycans and glycoproteins, covering the endothelium luminally. Both endothelium- and plasma-derived soluble molecules integrate into this mesh. Over the past decade, insight has been gained into the role of the glycocalyx in vascular physiology and pathology, including mechanotransduction, hemostasis, signaling, and blood cell–vessel wall interactions. The contribution of the glycocalyx to diabetes, ischemia/reperfusion, and atherosclerosis is also reviewed. Experimental data from the micro- and macrocirculation alludes at a vasculoprotective role for the glycocalyx. Assessing this possible role of the endothelial glycocalyx requires reliable visualization of this delicate layer, which is a great challenge. An overview is given of the various ways in which the endothelial glycocalyx has been visualized up to now, including first data from two-photon microscopic imaging