title: The rate of plasmin formation after in vitro clotting is inversely related to lipoprotein(a) plasma levels.
abstract: Lipoprotein(a) levels are largely genetically determined and are linked to increased risk of coronary artery disease. The hypothesis that elevated lipoprotein(a) levels lead to decreased fibrinolysis, due to the close structural homology with plasminogen, could in part explain the genesis of this risk, although contrasting results have been obtained in different studies. The aim of our study was to evaluate whether the rate of plasmin formation, enhanced in vitro by a fixed amount of human tissue plasminogen activator after clotting, was related to plasma lipoprotein(a) levels in 45 healthy subjects. Aliquots of human plasma were clotted with calcium chloride and thrombin followed by addition of tissue plasminogen activator. We then measured the time course of plasmin formation, determined as hydrolysis of H-D-valyl-L-leucyl-L-lysine-p-nitroanilide dihydrocortide (S-2251). The log of lipoprotein(a) level was negatively related to the rate of plasmin formation (r(s)=-0.46, P=0. 002), and multiple regression analysis indicated that this relationship was not influenced by the amount of plasminogen, fibrinogen, plasminogen activator inhibitor-1, tissue plasminogen activator, or by the size of apo(a) isoforms. These data support the concept that lipoprotein(a) can inhibit plasminogen activation and plasmin formation and can thereby play an important role in the genesis of atherosclerosis as an antifibrinolytic agent.
authors.affiliation: Istituto Nazionale di Riposo e Cura per Anziani V.E.II, Via S. Margherita, 5-60121 Ancona, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Testa
authors.forename: S M
authors.initials: SM
authors.lastname: Marcovina
mesh_terms: D000328:Adult; D001777:Blood Coagulation / Q000502:physiology*; D002863:Chromogenic Compounds / Q000378:metabolism; D003327:Coronary Disease / Q000097:blood / Q000209:etiology; D005260:Female; D005341:Fibrinolysin / Q000096:biosynthesis*; D005342:Fibrinolysis / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D017270:Lipoprotein(a) / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000378:metabolism; D012307:Risk Factors
chemical_list: D002863:Chromogenic Compounds; D017270:Lipoprotein(a); D009842:Oligopeptides; C018788:valyl-leucyl-lysine 4-nitroanilide; D005341:Fibrinolysin