Increased platelet thromboxane A2/prostaglandin H2 receptors in patients with acute myocardial infarction.
Platelets have been implicated in the formation of occlusive intracoronary thrombi leading to unstable angina pectoris and acute myocardial infarction. Evidence of platelet involvement in these syndromes includes increased thromboxane A2 synthesis during ischemic events and enhanced in vitro sensitivity to agonists. To determine the density and affinity of platelet thromboxane A2/prostaglandin H2 (TXA2/PGH2) receptors in patients with acute myocardial infarction and unstable angina pectoris, the maximum number of binding sites (Bmax) per platelet and the dissociation constant (Kd) of the TXA2/PGH2 receptor antagonist, [125I]-PTA-OH, was determined at equilibrium in washed platelets. Patients with acute myocardial infarction had a significantly (p = 0.006) higher Bmax (4,468 +/- 672 sites/platelet, n = 9) compared with controls (2,206 +/- 203 sites/platelet, n = 8). Restudied at a time when the patients' coronary artery disease was clinically stable, Bmax values for the myocardial infarction group had returned to within normal limits. The dissociation constant for [125I]-PTA-OH was not significantly different in the acute myocardial infarction patients compared with controls. In patients with acute myocardial infarction, the duration of chest pain was positively correlated (r = 0.71, p less than 0.02) with the number of [125I]-PTA-OH binding sites (Bmax). In vitro platelet sensitivity to the TXA2/PGH2 mimetic, U46619, was assessed in aggregation studies. The maximal velocity of aggregation (slope) correlated with platelet TXA2/PGH2 receptor number (r = 0.67, p less than 0.001) and was significantly higher (p less than 0.02) in the acute myocardial infarction patients compared with the other study groups. There was no significant difference in the aggregation EC50 values for the thromboxane mimetic U46619 between unstable angina, acute myocardial infarction, and control groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Dorn
G W
GW
Department of Cell and Molecular Pharmacology, Medical University of South Carolina, Charleston, SC 29425.
Liel
N
N
Trask
J L
JL
Mais
D E
DE
Assey
M E
ME
Halushka
P V
PV
D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood*; D010974:Platelet Aggregation; D011463:Prostaglandins H / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000378:metabolism*; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000378:metabolism; D013931:Thromboxanes / Q000378:metabolism
D011463:Prostaglandins H; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013931:Thromboxanes; D013928:Thromboxane A2; C046957:I-PTA-OH