Match!

Plasma Protein Oxidation as a Determinant of Impaired Fibrinolysis in Type 2 Diabetes

Published on Feb 1, 2019in Thrombosis and Haemostasis4.733
· DOI :10.1055/s-0038-1676609
Agata Hanna Bryk3
Estimated H-index: 3
(Jagiellonian University Medical College),
Konieczyńska M5
Estimated H-index: 5
+ 4 AuthorsAnetta Undas41
Estimated H-index: 41
(Jan Kochanowski University)
Abstract
Objective We investigated clinical and laboratory determinants of plasma protein oxidation and its associations with clot fibrinolysis in type 2 diabetes patients. Materials and Methods Our cross-sectional study consisted of 246 type 2 diabetic patients, 143 (58%) with concomitant cardiovascular disease (CVD), including 41 (17%) with previous myocardial infarction (MI). We measured total protein carbonylation (PC), thiobarbituric acid reactive substances (TBARS) and total antioxidant capacity (TAC) along with clot lysis time (CLT) and clot permeation (Ks ), fibrinogen, plasminogen, α-2-antiplasmin, plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI) and thrombomodulin. Results Total PC correlated positively, while TAC correlated inversely with glycated haemoglobin and diabetes duration (all p < 0.05). Diabetic patients with CVD had higher total PC, TBARS and lower TAC compared with the remainder (all p < 0.001). Among correlations of total PC with Ks , PAI-1, thrombomodulin and TAFI, the strongest was with CLT (r = 0.687, all p  Conclusion Elevated plasma PC, largely driven by a long history of diabetes and concomitant CVD, is an important determinant of hypofibrinolysis in type 2 diabetes.
  • References (32)
  • Citations (2)
📖 Papers frequently viewed together
3 Citations
78% of Scinapse members use related papers. After signing in, all features are FREE.
References32
Newest
#1Joanna CieslikH-Index: 1
#2Sandra Mrozinska (Jagiellonian University Medical College)H-Index: 4
Last. Anetta Undas (Jagiellonian University Medical College)H-Index: 41
view all 4 authors...
It has been demonstrated that fibrin clots generated from plasma samples obtained from patients with prior thromboembolic events are denser and less susceptible to lysis. Such a prothrombotic fibrin clot phenotype has been suggested as a new risk factor for venous thromboembolism, but its prognostic value is unclear. To assess whether abnormal clot properties can predict recurrent deep vein thrombosis (DVT), we studied 320 consecutive patients aged 18 to 70 years following the first-ever DVT. Pl...
21 CitationsSource
#1Markus Hecker (Heidelberg University)H-Index: 19
#2Andreas H. Wagner (Heidelberg University)H-Index: 14
Diabetes mellitus is a metabolic disease characterized by, among others, elevated blood glucose levels. Hyperglycaemia as well as enhanced levels of glucose-derived reactive metabolites contribute to the development of diabetic complications partly via increased generation of reactive oxygen species (ROS). ROS are not only part of signaling pathways themselves but also lead to carbonylation of particular amino acid side chains by direct metal-catalyzed oxidation. In addition, carbonyl groups can...
10 CitationsSource
#1Aslak Rautio (Umeå University)H-Index: 3
#2Kurt Boman (Umeå University)H-Index: 43
Last. Linda Mellbin (KI: Karolinska Institutet)H-Index: 16
view all 7 authors...
Introduction: Fibrinolytic factors, plasminogen activator inhibitor-1, tissue plasminogen activator, tissue plasminogen activator/plasminogen activator-complex and the haemostatic factor von Willeb ...
2 CitationsSource
#1Katherine J. Kearney (University of Leeds)H-Index: 2
#2Darren C. Tomlinson (University of Leeds)H-Index: 23
Last. Ramzi Ajjan (University of Leeds)H-Index: 33
view all 4 authors...
An enhanced thrombotic environment and premature atherosclerosis are key factors for the increased cardiovascular risk in diabetes. The occlusive vascular thrombus, formed secondary to interactions between platelets and coagulation proteins, is composed of a skeleton of fibrin fibres with cellular elements embedded in this network. Diabetes is characterised by quantitative and qualitative changes in coagulation proteins, which collectively increase resistance to fibrinolysis, consequently augmen...
12 CitationsSource
Abstract Hypoglycemia is the major barrier for optimal glycemic control in patients on maintenance insulin therapy. It is widely known that good glycemic control leads to prevention of or delay in the development of microvascular complications, and can reduce macrovascular events. It is thought that hypoglycemia may predispose patients to cognitive deterioration and may negatively affect the cardiovascular system. Hypoglycemia per se can contribute to a blunted counterregulatory response and dis...
4 CitationsSource
#1Massimo F. PiepoliH-Index: 74
#2Arno W. HoesH-Index: 85
Last. Simone BinnoH-Index: 8
view all 27 authors...
8 CitationsSource
#1R. J. King (University of Leeds)H-Index: 1
#2P. J. Grant (University of Leeds)H-Index: 1
Diabetes is associated with the development of premature cardiovascular disease (CVD), which relates to the clustering of risk factors such as dyslipidaemia, hypertension, obesity and hyperglycaemia in the presence of insulin resistance. In addition, diabetes is associated with an inflammatory and pro-thrombotic environment, exacerbating the development of atherothrombosis. Insulin resistance and hyperglycaemia both contribute to the development of endothelial cell dysfunction and increased oxid...
21 CitationsSource
Aims. We sought to investigate whether enhanced oxidation contributes to unfavorable fibrin clot properties in patients with diabetes. Methods. We assessed plasma fibrin clot permeation (Ks, a measure of the pore size in fibrin networks) and clot lysis time induced by recombinant tissue plasminogen activator (CLT) in 163 consecutive type 2 diabetic patients (92 men and 71 women) aged 65 ± 8.8 years with a mean glycated hemoglobin (HbA1c) of 6.8%. We also measured oxidative stress markers, includ...
8 CitationsSource
Type 2 diabetes mellitus (T2DM) is a major cardiovascular risk factor. Persistent platelet activation plays a key role in atherothrombosis in T2DM. However, current antiplatelet treatments appear less effective in T2DM patients vs nondiabetics at similar risk. A large body of evidence supports the contention that oxidative stress, which characterizes DM, may be responsible, at least in part, for less-than-expected response to aspirin, with multiple mechanisms acting at several levels. This revie...
28 CitationsSource
#1Matteo Becatti (UniFI: University of Florence)H-Index: 21
#2Rossella Marcucci (UniFI: University of Florence)H-Index: 44
Last. Claudia Fiorillo (UniFI: University of Florence)H-Index: 23
view all 10 authors...
Objective— Among plasma proteins, fibrinogen represents a major target of oxidative modifications. In patients with post–acute myocardial infarction (6 months after the acute event), fibrinogen oxidation-induced carbonyls and fibrinogen function were estimated using in vitro and ex vivo approaches. Fibrinogen structural features and clot architecture were also explored. Approach and Results— In 39 patients with post–acute myocardial infarction and 28 age-, sex-, and risk factor-matched controls,...
39 CitationsSource
Cited By2
Newest
#1Maciej Polak (Jagiellonian University Medical College)H-Index: 4
#2Jakub Siudut (Jagiellonian University Medical College)H-Index: 5
Last. Anetta Undas (Jagiellonian University Medical College)H-Index: 41
view all 4 authors...
Venous ulcers are the most severe manifestation of post-thrombotic syndrome (PTS). We have previously demonstrated that formation of compact fibrin clots resistant to lysis is observed in patients following deep-vein thrombosis (DVT) who developed PTS. The current study investigated whether unfavourable fibrin clot properties can predict post-thrombotic venous ulcers. In a cohort study on 186 consecutive patients following DVT, we determined plasma fibrin clot characteristics, including clot per...
Source
#1Bowen Li (Jiangnan University)H-Index: 1
#2Ling Mo (Jiangnan University)H-Index: 1
Last. Guowei Le (Jiangnan University)H-Index: 24
view all 9 authors...
This study explored the effects of protein oxidation during milk processing on spatial learning and memory in rats. Increasing the heating time, fat content, and inlet air temperature during processing by boiling, microwave heating, spray-drying, or freeze-drying increases milk protein oxidation. Oxidative damage done to milk proteins by microwave heating is greater than that caused by boiling. Dityrosine (DT), as a kind of tyrosine oxidation product, is the most important marker of this process...
Source