Dyslipidemias and fibrinolysis.
BACKGROUND
The relation between fibrinolysis and cardiovascular disease is an open debate. Fibrinolysis is related to endothelial function and presents many molecular links with platelet and coagulation activity. Furthermore, reduced fibrinolysis has been reported in several dysmetabolic conditions.


METHODS
To detect mechanisms linking dyslipidemias and fibrinolysis we evaluated 75 subjects (42 males, 33 females, 20 hypercholesterolemic, 20 hypertriglyceridemic or 20 with mixed hyperlipoproteinemia, 15 with isolated low HDL-cholesterol). Plasminogen activator inhibitor (PAI)-1, tissue-type plasminogen activator activity and plasmin-antiplasmin complexes (PAP) were determined at baseline and after the venous occlusion test. We also measured D-dimer, lipid pattern, soluble E-selectin, platelet surface P-selectin, prothrombin fragments 1 + 2 (F1 + 2), lipoprotein(a), factor VII, von Willebrand factor, plasma insulin, fibrinogen, homocysteine, thrombin activable fibrinolysis inhibitor (TAFI) activity, thrombomodulin, factor XIII, urokinase-type plasminogen activator.


RESULTS
Hypertriglyceridemic patients were found to have lower PAP and D-dimer and higher PAI-1 serum levels (baseline and venous occlusion test, p < 0.001 and p < 0.01) compared to hypercholesterolemic and control subjects (p < 0.01, p < 0.001). P-selectin, F1 + 2 and TAFI were significantly increased only in hypercholesterolemic subjects (p < 0.001) and associated with reduced PAP and D-dimer, showing a linear relation with LDL-cholesterol levels (p < 0.01, r = -0.62 and p < 0.01, r = -0.59). PAI-1 activity was not different with respect to controls (baseline p = 0.59, venous occlusion test p = 0.42). Serum levels of von Willebrand factor were significantly increased in hypertriglyceridemic/low HDL subjects compared to hypercholesterolemics (p < 0.01).


CONCLUSIONS
Impaired fibrinolysis in subjects with hypertriglyceridemia/low HDL-cholesterol is associated with increased serum levels of PAI-1 whereas enhanced thrombin generation and TAFI hyperactivity are the main findings in hypercholesterolemia. Such data may suggest the opportunity of evaluating several fibrinolytic factors when studied as prognostic factors in diverse dyslipidemias.
Puccetti
Luca
L
Department of Clinical Medicine and Immunological Sciences, Section of Medical Semeiotics, Center for Metabolic Diseases and Atherosclerosis, University of Siena, Siena, Italy. puccetti@unisi.it
Bruni
Fulvio
F
Pasqui
Anna Laura
AL
Pastorelli
Marcello
M
Bova
Giovanni
G
Cercignani
Michela
M
Palazzuoli
Alberto
A
Auteri
Alberto
A
D000328:Adult; D019040:E-Selectin / Q000378:metabolism*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood*; D015228:Hypertriglyceridemia / Q000097:blood; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism; D011498:Protein Precursors / Q000378:metabolism; D011516:Prothrombin / Q000378:metabolism; D014841:von Willebrand Factor / Q000378:metabolism*
D019040:E-Selectin; D005338:Fibrin Fibrinogen Degradation Products; D019007:P-Selectin; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D011498:Protein Precursors; C036309:fibrin fragment D; D014841:von Willebrand Factor; C029733:prothrombin fragment 1; D011516:Prothrombin