carboxypeptidase-b and Atherosclerosis

Gouty arthritis (GA) is a chronic inflammatory arthritis in which both clinical and subclinical atherosclerosis are more frequent. The dynamic equilibrium between coagulation and fibrinolysis is impaired in inflammatory diseases. We determined TFPI and TAFI antigen levels in GA patients and evaluated their association with subclinical atherosclerosis.. We included 45 GA patients (41 males, 4 females; mean age: 51.6years) and 25 asymptomatic hyperuricemic (AHU) subjects (19 males, 6 females; mean age: 48.1years). Cardiovascular risk factors were determined. TAFI and TFPI levels were determined by ELISA. B-mode ultrasonography was used to detect subclinical atherosclerosis.. Cardiovascular risk factors were similar in both groups. The carotid IMT was significantly higher in GA group than in AHU group (0.74±0.23mm vs. 0.61±0.13mm, p=0.009). TFPI level was significantly higher in GA group than in AHU group (86.2±48.9ng/mL vs. 25.8±21.4ng/mL, p<0.001); TAFI antigen was significantly higher in AHU group (22.6±3.6ng/mL vs. 25.7±5.3ng/mL, p=0.006) than in GA patients. Atherosclerotic plaque formation was more frequent in GA group (p=0.041). When GA patients with and without plaques were compared, the first group had significantly higher mean age (p=0.01) and TFPI level (p=0.028). TFPI level correlated with carotid IMT (r=0.302; p=0.028). Logistic regression analysis showed that age (OR: 1.236, 95%CI: 1.059-1.443, p=0.007) and TFPI (OR: 1.031, 95%CI: 1.008-1.054, p=0.008) were independent risk factors for the presence of plaques.. GA patients had more frequent subclinical atherosclerosis than subjects with AHU. Higher TFPI levels in GA patients -probably associated with enhanced endothelial damage- were related to subclinical atherosclerosis. Lower TAFI levels in GA pointed to impaired fibrinolysis.

Topics: Adult; Aged; Arthritis, Gouty; Atherosclerosis; Carboxypeptidase B; Female; Humans; Lipoproteins; Male; Middle Aged; Thrombin

Besides having a key role in fibrinolysis, the plasminogen system has been implicated in cell migration and angiogenesis. A common mechanism is the binding of plasminogen to carboxy-terminal lysine residues in partially degraded fibrin or on cellular surfaces. Here we examined the involvement of thrombin activatable fibrinolysis inhibitor (TAFI) and pancreatic carboxypeptidase B (CPB) in an in vitro capillary tube formation system, which is largely plasminogen-dependent.. Human microvascular endothelial cells (hMVECs) were seeded on a 3D plasma clot matrix and subsequently stimulated with bFGF/tumor necrosis factor (TNF)-alpha. Tube formation was analyzed and fibrin degradation products (FbDP) were determined in the medium. Supplementation of the matrix with additional TAFI or CPB produced a reduction in tube formation. Pretreatment of hMVECs with CPB before seeding resulted in a similar effect. FbDP-levels indicated a concomitant reduction in matrix proteolysis. A TAFIa inhibitor increased tube formation and FbDP release into the medium. In separate assays, CPB impaired the migration of hMVECs in a dose-dependent manner, whereas proliferation and adhesion remained unaffected.. Overall, these results demonstrate that TAFI and CPB in these systems modulate the plasminogen system both in the matrix and on the cell surface, thus leading to the inhibition of endothelial cell movement and tube formation.

Topics: Angiogenesis Inhibitors; Atherosclerosis; Capillaries; Carboxypeptidase B; Carboxypeptidase B2; Cell Adhesion; Cell Culture Techniques; Cell Movement; Cell Proliferation; Cells, Cultured; Dose-Response Relationship, Drug; Endothelial Cells; Fibrin; Fibrin Fibrinogen Degradation Products; Fibroblast Growth Factor 2; Humans; Neovascularization, Physiologic; Plant Proteins; Plasminogen; Protease Inhibitors; Time Factors; Tumor Necrosis Factor-alpha; Urokinase-Type Plasminogen Activator; Wound Healing