Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.36 (hyaluronidase)
 4,606 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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. To establish whether glycocalyx is associated with microvascular damage, we performed glycocalyx perturbation volume measurements in type 1 diabetic patients with microalbuminuria (DM1-MA group; n = 7), without microalbuminuria (DM1-NA group; n = 7), and in age-matched control subjects (CON; n = 7). Systemic glycocalyx volume was determined comparing intravascular distribution volume of a glycocalyx-permeable tracer (dextran 40) to that of a glycocalyx-impermeable tracer (labeled erythrocytes). Sublingual capillaries were visualized using orthogonal polarization spectral microscopy to estimate microvascular glycocalyx. Patients and control subjects were matched according to age and BMI. Glycocalyx volume decreased in a stepwise fashion from CON, DM1-NA, and finally DM1-MA subjects (1.5 +/- 0.1, 0.8 +/- 0.4, and 0.2 +/- 0.1 l, respectively, P < 0.05). Microvascular glycocalyx in sublingual capillaries was also decreased in type 1 diabetes versus the control group (0.5 +/- 0.1 vs. 0.9 +/- 0.1 microm, P < 0.05). Plasma hyaluronan, a principal glycocalyx constituent, and hyaluronidase were increased in type 1 diabetes. In conclusion, type 1 diabetic patients are characterized by endothelial glycocalyx damage, the severity of which is increased in presence of microalbuminuria.
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PMID:Endothelial glycocalyx damage coincides with microalbuminuria in type 1 diabetes. 1656 38

Changes in the extracellular matrix organization within vascular walls are critical events in the process of atherosclerosis including diabetic macroangiopathy. Here, we examined whether glucose can directly modulate connective tissue reorganization by human vascular smooth muscle cells (VSMCs). Using a collagen gel contraction (CGC) assay, we demonstrated that in comparison with normal glucose concentration (5 mM), high glucose concentration (25 mM) inhibits the efficacy of VSMCs to contract collagen gels. With human genome microarrays, we showed a significant increase in the expression of hyaluronan synthase 2 (HAS2) by VSMCs in hyperglycemic conditions. The finding was verified with quantitative real-time polymerase chain reaction, which also revealed that the expression of the other hyaluronan synthesizing enzymes, HAS1 and HAS3, was stimulated concomitantly. A corresponding increase was observed in hyaluronan (HA) production. Treatment of VSMCs either with hyaluronidase or with 4-methylumbelliferone, an inhibitor of HA synthesis, partially restored the diminished CGC efficacy of VSMCs in hyperglycemic conditions. In conclusion, high glucose concentration stimulated HA synthesis by VSMCs and modulated their ability to reorganize collagen-rich matrix. Because HA is known to enhance the development of atherosclerosis and restenosis after percutaneous coronary interventions, our study provides a new potential mechanism whereby hyperglycemia leads to disturbed vascular remodeling in diabetic patients through stimulation of HA synthesis.
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PMID:Hyperglycemic conditions modulate connective tissue reorganization by human vascular smooth muscle cells through stimulation of hyaluronan synthesis. 2048 39