Plasmatic nitric oxide, but not von Willebrand Factor, is an early marker of endothelial damage, in type 1 diabetes mellitus patients without microvascular complications

Background. The adverse impact of chronic hyperglycaemia on vascular wall in diabetes mellitus includes endothelial dysfunction with subsequent development of diabetic microangiopathy. Microangiopathy can be corrected via adequate glycaemic control for establishing a target level of glycated haemoglobin. Considering a multiplex nature of metabolic and vascular regulation, a comprehensive approach is required for simultaneous correction of rheological disorders, hypercoagulation and endothelial dysfunction.Objectives. Estimation of vascular factors (von Willebrand factor, desquamated endothelium, antithrombin III, protein C, VEGF) and capillaroscopic patterns in therapy for type 1 diabetes with methylethylpyridinol in comparison with sulodexide.Methods. A total of 89 patients with type 1 diabetes were examined and separated by two cohorts: 42 patients receiving sulodexide (cohort 1) and 47 patients receiving methylethylpyridinol (cohort 2). Therapy duration was 14 days. Both cohorts were estimated pre- and post-treatment endothelial conditions (activity of von Willebrand factor, VEGF, desquamated endothelial cell count), anticoagulant indicators (activity of antithrombin III, protein C) and had capillaroscopy with functional test and oximetry.Results. Diabetes patients in pre-treatment exhibited signs of endothelial dysfunction, reduced blood anticoagulant protection and capillary constriction. Both cohorts in post-treatment showed the signiﬁcantly reduced von Willebrand factor, VEGF activity and desquamated endothelial cell count. The anticoagulant system revealed positive dynamics; capillaroscopy reported limiting of the capillary transition zonal diameter and a certain improvement in functional performance.Conclusion. Patients with type 1 diabetes were revealed with endothelial dysfunction and an increased blood procoagulant activity. Both sulodexide and methylethylpyridinol treatments improved endothelial dysfunction and anticoagulant blood protection. Both preparations can be used for complex microangiopathy correction in patients with <10-years history of type 1 diabetes mellitus.

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Retinal vascular fractals predict long-term microvascular complications in type 1 diabetes mellitus: the Danish Cohort of Pediatric Diabetes 1987 (DCPD1987)

Diabetologia ◽

10.1007/s00125-014-3317-6 ◽

2014 ◽

Vol 57 (10) ◽

pp. 2215-2221 ◽

Cited By ~ 31

Author(s):

Rebecca Broe ◽

Malin L. Rasmussen ◽

Ulrik Frydkjaer-Olsen ◽

Birthe S. Olsen ◽

Henrik B. Mortensen ◽

...

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Microvascular Complications ◽

Pediatric Diabetes ◽

Danish Cohort

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Diabetic Pregnancy: Maternal Metabolic and Microvascular Complications in Type 1 Diabetes mellitus

Frontiers in Diabetes, 2005 - Diabetology of Pregnancy ◽

10.1159/000087427 ◽

2005 ◽

pp. 254-270

Author(s):

Donald W.M. Pearson

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Microvascular Complications ◽

Diabetic Pregnancy

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Clustering of microvascular complications in Type 1 diabetes mellitus

Journal of Diabetes and its Complications ◽

10.1016/j.jdiacomp.2018.01.011 ◽

2018 ◽

Vol 32 (4) ◽

pp. 393-399 ◽

Cited By ~ 6

Author(s):

Lasse Bjerg ◽

Adam Hulman ◽

Morten Charles ◽

Marit Eika Jørgensen ◽

Daniel Rinse Witte

Keyword(s):

Diabetes Mellitus ◽

Type 1 Diabetes ◽

Type 1 Diabetes Mellitus ◽

Microvascular Complications

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Insights Into Immunothrombosis: The Interplay Among Neutrophil Extracellular Trap, von Willebrand Factor, and ADAMTS13

Frontiers in Immunology ◽

10.3389/fimmu.2020.610696 ◽

2020 ◽

Vol 11 ◽

Author(s):

Junxian Yang ◽

Zhiwei Wu ◽

Quan Long ◽

Jiaqi Huang ◽

Tiantian Hong ◽

...

Keyword(s):

Von Willebrand Factor ◽

Therapeutic Strategy ◽

Endothelial Activation ◽

Endothelial Damage ◽

Neutrophil Extracellular Trap ◽

Activated Neutrophils ◽

A Disintegrin And Metalloproteinase ◽

Von Willebrand ◽

Willebrand Factor

Both neutrophil extracellular traps (NETs) and von Willebrand factor (VWF) are essential for thrombosis and inflammation. During these processes, a complex series of events, including endothelial activation, NET formation, VWF secretion, and blood cell adhesion, aggregation and activation, occurs in an ordered manner in the vasculature. The adhesive activity of VWF multimers is regulated by a specific metalloprotease ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motifs, member 13). Increasing evidence indicates that the interaction between NETs and VWF contributes to arterial and venous thrombosis as well as inflammation. Furthermore, contents released from activated neutrophils or NETs induce the reduction of ADAMTS13 activity, which may occur in both thrombotic microangiopathies (TMAs) and acute ischemic stroke (AIS). Recently, NET is considered as a driver of endothelial damage and immunothrombosis in COVID-19. In addition, the levels of VWF and ADAMTS13 can predict the mortality of COVID-19. In this review, we summarize the biological characteristics and interactions of NETs, VWF, and ADAMTS13, and discuss their roles in TMAs, AIS, and COVID-19. Targeting the NET-VWF axis may be a novel therapeutic strategy for inflammation-associated TMAs, AIS, and COVID-19.

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