Plasminogen and plasmin activity in patients with coronary artery disease.
OBJECTIVE
While coronary artery disease (CAD) is associated with disturbances of the plasma fibrinolytic system, the nature of these disturbances is not fully defined. Fibrinolysis is regulated by plasmin, whose production is mediated by plasminogen activator conversion of plasminogen (Plg) to plasmin. The cascade is modulated by feedback loops that include Plg activator inhibitor 1 (PAI-1). Molecular interactions with Plg kringle domains play an important role in regulating plasmin production and its modulation of fibrinolysis. We hypothesized that interactions of tissue plasminogen activator (tPA) with Plg kringle domains regulates plasmin levels in patients with stable CAD.


METHODS
Plasma was collected from patients (n = 33) with an angiographically significant CAD and controls (n = 18) with angiographically established normal or minimally diseased arteries. Plasmin activity, tPA activity, and plasma levels of Plg, PAI-1, uPA, and tPA were determined.


RESULTS
CAD patients had 1.7-fold greater plasmin activity (P = 0.02) that correlated with 1.5-fold higher tPA activity when compared to controls. Epitope mapping of Plg domains showed Plg differences in epitope exposure between the two groups. Plasma from CAD patients had 50% less (P < 0.001) detectable kringle 4 and 48% less (P = 0.007) detectable kringles 1-3.


CONCLUSIONS
Based on detectable differences in Plg, we conclude that in patients with stable CAD, Plg complexed with tPA exists in a conformation that enables increased tPA activity and Plg conversion to plasmin.
Drinane
M C
MC
Department of Surgery, Vascular Section, Dartmouth Medical School, Lebanon, NH 03756, USA.
Sherman
J A
JA
Hall
A E
AE
Simons
M
M
Mulligan-Kehoe
M J
MJ
D000293:Adolescent; D000328:Adult; D003324:Coronary Artery Disease / Q000097:blood / Q000201:enzymology*; D018604:Epitope Mapping; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005341:Fibrinolysin / Q000378:metabolism*; D006801:Humans; D018082:Kringles; D008297:Male; D010949:Plasma / Q000378:metabolism; D010958:Plasminogen / Q000737:chemistry / Q000378:metabolism*; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011485:Protein Binding; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000378:metabolism*; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood
D005338:Fibrin Fibrinogen Degradation Products; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; C036309:fibrin fragment D; D010958:Plasminogen; D010959:Tissue Plasminogen Activator; D005341:Fibrinolysin; D014568:Urokinase-Type Plasminogen Activator