The level of circulating fibroblast activation protein correlates with incorporation of alpha-2-antiplasmin into the fibrin clot

Willige, Shirley Uitte de; Abdul, Shiraazkhan; Leebeek, Frank W.G.; Rijken, D.C.

doi:10.1016/j.thromres.2018.03.018

Cited by 13 publications

(12 citation statements)

References 17 publications

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“…Interestingly, α2-antiplasmin incubation with glucose in similar conditions as above was associated with decreased α2-antiplasmin binding affinity to fibrin [ 107 ]. This finding seems to be counterintuitive to previous reports showing increased FXIII-induced cross-linkage of α2-antiplasmin to fibrin when compared to control subjects both in fibrin from fibrinogen purified from T2DM patients (by 20%) [ 21 ] and in a plasma-based assay (by 6%) [ 108 ]. It appears that the results strongly depend on the model chosen for investigation, with plasma-based assays probably being the most appropriate.…”

Section: Mechanisms Of Hypofibrinolysis In T2dmcontrasting

confidence: 96%

Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation

Bryk-Wiązania

Undas

2021

Cardiovasc Diabetol

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A prothrombotic state is a typical feature of type 2 diabetes mellitus (T2DM). Apart from increased platelet reactivity, endothelial dysfunction, hyperfibrinogenemia, and hypofibrinolysis are observed in T2DM. A variety of poorly elucidated mechanisms behind impaired fibrinolysis in this disease have been reported, indicating complex associations between platelet activation, fibrin formation and clot structure, and fibrinolysis inhibitors, in particular, elevated plasminogen antigen inhibitor-1 levels which are closely associated with obesity. Abnormal fibrin clot structure is of paramount importance for relative resistance to plasmin-mediated lysis in T2DM. Enhanced thrombin generation, a proinflammatory state, increased release of neutrophil extracellular traps, elevated complement C3, along with posttranslational modifications of fibrinogen and plasminogen have been regarded to contribute to altered clot structure and impaired fibrinolysis in T2DM. Antidiabetic agents such as metformin and insulin, as well as antithrombotic agents, including anticoagulants, have been reported to improve fibrin properties and accelerate fibrinolysis in T2DM. Notably, recent evidence shows that hypofibrinolysis, assessed in plasma-based assays, has a predictive value in terms of cardiovascular events and cardiovascular mortality in T2DM patients. This review presents the current data on the mechanisms underlying arterial and venous thrombotic complications in T2DM patients, with an emphasis on hypofibrinolysis and its impact on clinical outcomes. We also discuss potential modulators of fibrinolysis in the search for optimal therapy in diabetic patients.

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Section: Mechanisms Of Hypofibrinolysis In T2dmcontrasting

confidence: 96%

Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation

Bryk-Wiązania

Undas

2021

Cardiovasc Diabetol

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“…Patients with T2DM have been reported by several groups to display enhanced thrombin generation in comparison to controls [28][29][30], and a more hypercoagulable clot has been reported in apparently healthy female subjects as compared with men [4]. Since 90% of α2-antiplasmin incorporation is FXIII-dependent [8], and FXIII becomes activated by thrombin [6], it would be expected that women with T2DM who have increased α2antiplasmin incorporation could demonstrate increased thrombin generation as compared with men. Indeed in the present study, female diabetic patients were characterized by faster formation of the total amounts of thrombin (which can be generated in a plasma sample) when compared with male subjects.…”

Section: Discussionmentioning

confidence: 99%

“…Recently, increased α2-antiplasmin incorporation has been shown using a plasma-based clotting assay in young patients with diabetes (unspecified type) following myocardial infarction (MI) or ischemic stroke [8]. It is unknown whether there are any differences in this reaction between men and women with T2DM.…”

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confidence: 99%

Sex-specific alteration to α2-antiplasmin incorporation in patients with type 2 diabetes

Bryk

Siudut

Broniatowska

et al. 2020

Thrombosis Research

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A B S T R A C TBackground: Type 2 diabetes mellitus (T2DM) is associated with hypofibrinolysis and increased factor XIIImediated α2-antiplasmin incorporation into the fibrin clot. It is unclear whether there are sex-related differences in α2-antiplasmin incorporation in relation to impaired clot lysis in T2DM. Aim: We investigated α2-antiplasmin incorporation into fibrin clots as a determinant of clot lysability in patients of both sexes with T2DM. Methods: In a group of 113 T2DM patients, 54 (47.8%) of which were women, we investigated α2-antiplasmin incorporation using an in-house sandwich enzyme-linked immunoassay and plasma clot lysis by turbidimetry, along with fibrinogen and thrombin generation using calibrated automated thrombogram and factor XIII activity. Results: Female patients had 15.2% greater α2-antiplasmin incorporation into the fibrin clot (p = 0.008) and slightly higher plasma α2-antiplasmin concentration (p = 0.005) along with 8.4% longer time to 50% lysis (Lys50 MA , p = 0.012) compared with men. Female patients had enhanced thrombin generation represented by shorter lag phase (p = 0.042), shorter time to peak (p = 0.033), and higher endogenous thrombin potential (p = 0.003) compared with men, while factor XIII activity was comparable between sexes (p = 0.085). On multivariate regression, patient sex and glycated hemoglobin (HbA1c) level were the predictors of α2-antiplasmin incorporation in the entire patient group, while α2-antiplasmin incorporation was associated with Lys50 MA , as were fibrinogen, male sex and body-mass index. Conclusions: This study suggests that a more compromised fibrinolysis in diabetic women when compared with men could be in part mediated by increased α2-antiplasmin incorporation into the fibrin.

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“…Indirect evidence of collagen deposition or fiber formation can be derived from the evaluation of fibroblast activation. As a result, it determines when fibrosis can still be prevented and the course of the disease altered ( 43 , 44 ). According to Stein S et al, constitutive deletion of FAP decreases experimental atherosclerosis progression and increases plaque stability with reduced collagen breakdown ( 45 ).…”

Section: Discussionmentioning

confidence: 99%

A clinical study on relationship between visualization of cardiac fibroblast activation protein activity by Al18F-NOTA-FAPI-04 positron emission tomography and cardiovascular disease

Lyu

Han

Zhao

et al. 2022

Front. Cardiovasc. Med.

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ObjectiveFAP plays a vital role in myocardial injury and fibrosis. Although initially used to study imaging of primary and metastatic tumors, the use of FAPI tracers has recently been studied in cardiac remodeling after myocardial infarction. The study aimed to investigate the application of FAPI PET/CT imaging in human myocardial fibrosis and its relationship with clinical factors.Materials and methodsRetrospective analysis of FAPI PET/CT scans of twenty-one oncological patients from 05/2021 to 03/2022 with visual uptake of FAPI in the myocardium were applying the American Heart Association 17-segment model of the left ventricle. The patients’ general data, echocardiography, and laboratory examination results were collected, and the correlation between PET imaging data and the above data was analyzed. Linear regression models, Kendall’s TaU-B test, the Spearman test, and the Mann–Whitney U test were used for the statistical analysis.Results21 patients (60.1 ± 9.4 years; 17 men) were evaluated with an overall mean LVEF of 59.3 ± 5.4%. The calcific plaque burden of LAD, LCX, and RCA are 14 (66.7%), 12 (57.1%), and 9 (42.9%). High left ventricular SUVmax correlated with BMI (P < 0.05) and blood glucose level (P < 0.05), and TBR correlated with age (P < 0.05). A strong correlation was demonstrated between SUVmean and CTnImax (r = 0.711, P < 0.01). Negative correlation of SUVmean and LVEF (r = −0.61, P < 0.01), SUVmax and LVEF (r = −0.65, P < 0.01) were found. ROC curve for predicting calcified plaques by myocardial FAPI uptake (SUVmean) in LAD, LCX, and RCA territory showed AUCs were 0.786, 0.759, and 0.769.ConclusionFAPI PET/CT scans might be used as a new potential method to evaluate cardiac fibrosis to help patients’ management further. FAPI PET imaging can reflect the process of myocardial fibrosis. High FAPI uptakes correlate with cardiovascular risk factors and the distribution of coronary plaques.

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The level of circulating fibroblast activation protein correlates with incorporation of alpha-2-antiplasmin into the fibrin clot

Cited by 13 publications

References 17 publications

Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation

Hypofibrinolysis in type 2 diabetes and its clinical implications: from mechanisms to pharmacological modulation

Sex-specific alteration to α2-antiplasmin incorporation in patients with type 2 diabetes

A clinical study on relationship between visualization of cardiac fibroblast activation protein activity by Al18F-NOTA-FAPI-04 positron emission tomography and cardiovascular disease

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