1. Thrombin-activatable fibrinolysis inhibitor in human abdominal aortic aneurysm disease.
- Author
-
Bridge KI, Bollen L, Zhong J, Hesketh M, Macrae FL, Johnson A, Philippou H, Scott DJ, Gils A, and Ariёns RAS
- Subjects
- Aged, Aged, 80 and over, Aortic Aneurysm, Abdominal diagnostic imaging, Aortic Aneurysm, Abdominal enzymology, Biomarkers blood, Case-Control Studies, Enzyme Activation, Enzyme-Linked Immunosorbent Assay, Female, Fibrinolysin analysis, Humans, Male, Middle Aged, Peptides blood, alpha-2-Antiplasmin analysis, Aortic Aneurysm, Abdominal blood, Carboxypeptidase B2 blood
- Abstract
Essentials Patients with abdominal aortic aneurysms (AAA) develop dense clots that are resistant to lysis. This study explores the role of thrombin-activatable fibrinolysis inhibitor (TAFI) in human AAA. There is evidence of chronically increased TAFI activation in patients with AAA. TAFI may represent a pharmacological target for cardiovascular risk reduction in AAA., Summary: Background Intra-luminal thrombosis is a key factor in growth of abdominal aortic aneurysms (AAAs). Patients with AAA form dense clots that are resistant to fibrinolysis. Thrombin-activatable fibrinolysis inhibitor (TAFI) has been shown to influence AAA development in murine models. Objective The aim of this study is to characterize the role of TAFI in human AAA. Methods Plasma levels of TAFI, TAFI activation peptide (TAFI-AP), activated/inactivated TAFI (TAFIa/ai) and plasmin-α2-antiplasmin complex were measured by ELISAs in patients with AAA (n = 202) and controls (n = 188). Results TAFIa/ai and TAFI-AP levels were higher in patients than controls (median [IQR], 20.3 [14.6-32.8] ng mL
-1 vs. 14.2 [11.2-19.3] ng mL-1 and 355.0 [232.4-528.1] ng mL-1 vs. 248.6 [197.1-328.1] ng mL-1 ). TAFIa/ai was positively correlated with TAFI-AP (r = 0.164). Intact TAFI levels were not different between patients and controls (13.4 [11.2-16.1] μg mL-1 vs. 12.8 [10.6-15.4] μg mL-1 ). Plasmin-α2-antiplasmin was higher in AAA patients than controls (690.0 [489.1-924.3] ng mL-1 vs. 480.7 [392.6-555.3] ng mL-1 ). Conclusions The increase in TAFIa/ai and TAFI-AP suggests an increased TAFI activation in patients with AAA. Prospective studies are required to further elucidate the role of TAFI and fibrinolysis in AAA pathogenesis., (© 2017 International Society on Thrombosis and Haemostasis.)- Published
- 2017
- Full Text
- View/download PDF