Effects of lipoprotein(a) on in vitro lysis of whole blood thrombi from healthy volunteers.
Elevated levels of lipoprotein(a) [Lp(a)] were shown to be an independent cardiovascular risk factor. Structural homologies between Lp(a) and plasminogen could be of importance for this. In the present study, the influence of Lp(a) on in vitro lysis of thrombi produced in recalcified whole blood was investigated. Of 120 healthy volunteers, 21 (18%) had serum Lp(a) levels > or = 25 mg/dl (median 70 mg/dl). Compared to 46 controls with serum Lp(a) < 25 mg/dl (median 7 mg/dl), the weight of whole blood thrombi generated in vitro was similar (96 +/- 11 vs. 94 +/- 13 mg). Thrombolysis with exogenously added tissue plasminogen activator (TPA; 0.1, 0.4 and 1.6 mg/l) was not affected by the ex vivo concentration of Lp(a). In persons with elevated Lp(a), plasma TPA levels were higher than in persons with low Lp(a) [15.7 +/- 1.5 vs. 11.7 +/- 1.2 micrograms/l; p = 0.051], but plasminogen activator inhibitor (PAI) activity and the plasma concentrations of PAI-1 were also higher. When Lp(a) was added in vitro to blood with low baseline Lp(a) [median final concentration 47 mg/dl], thrombolysis was significantly inhibited with low doses of TPA (0.1 and 0.4 mg/l), but remained unaffected with TPA 1.6 mg/l. Thus, the inhibitory effect of Lp(a) on thrombolysis seems to be counterregulated in blood of healthy volunteers with elevated Lp(a).
Terres
W
W
Department of Cardiology, Eppendorf University Hospital, Hamburg, Federal Republic of Germany.
Krewitt
M
M
Hamm
C W
CW
D000328:Adult; D001780:Blood Coagulation Tests; D004305:Dose-Response Relationship, Drug; D005260:Female; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D017270:Lipoprotein(a) / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D010959:Tissue Plasminogen Activator / Q000097:blood
D017270:Lipoprotein(a); D010959:Tissue Plasminogen Activator