Increased platelet binding to circulating monocytes in acute coronary syndromes.
BACKGROUND
Present therapies for acute coronary syndromes aim toward limiting platelet-platelet adhesion and aggregation processes. However, platelet-leukocyte interactions may contribute importantly to disease progression in the arterial wall. Recent studies suggest that prevention of platelet-leukocyte binding via P-selectin glycoprotein ligand-1 (PSGL-1) may be beneficial in animal models of vascular injury.


RESULTS
P-selectin-PSGL-1 interactions were found to account for most platelet-monocyte binding observed in peripheral blood samples from healthy donors. However, a significant component of observed adhesion was calcium independent, involving neither PSGL-1 nor P-selectin. Platelet-monocyte interactions were examined in 52 patients admitted within 14 hours of symptom onset, with acute coronary syndromes defined as unstable angina (n=12) and acute myocardial infarction (n=13) or noncardiac chest pain (n=27). When compared with patients with noncardiac chest pain, significantly elevated levels of platelet-monocyte binding were found in patients with acute myocardial infarction (70.1+/-15.4% versus 45.4+/-23.3%; P<0.01) and unstable angina (67.4+/-12.9% versus 45.4+/-23.3%; P>0.01). Calcium-independent platelet-monocyte binding was significantly elevated in myocardial infarction patients alone (14.7+/-7.7% versus 6.1+/-5.96%; P<0.001).


CONCLUSIONS
There is evidence for a significant P-selectin-independent molecular component to the platelet-monocyte conjugation observed in peripheral blood. Patients with myocardial infarction and unstable angina demonstrate increased total binding of platelets to monocytes. Additionally, calcium-independent adhesion was significantly elevated in patients with evidence of myocardial infarction. These findings demonstrate that novel cation-independent adhesion mechanisms may mediate platelet-monocyte binding, representing a new therapeutic target after vascular injury associated with myocardial infarction.
Sarma
Jaydeep
J
Medical Research Council Centre for Inflammation Research, University of Edinburgh Medical School, Edinburgh, UK. j.sarma@ed.ac.uk
Laan
Caterina A
CA
Alam
Shirjel
S
Jha
Ashwani
A
Fox
Keith A A
KA
Dransfield
Ian
I
D000328:Adult; D000789:Angina, Unstable / Q000097:blood*; D001792:Blood Platelets / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000502:physiology; D002448:Cell Adhesion; D002637:Chest Pain / Q000097:blood / Q000175:diagnosis; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology; D008875:Middle Aged; D009000:Monocytes / Q000166:cytology / Q000502:physiology*; D009203:Myocardial Infarction / Q000097:blood*; D019007:P-Selectin / Q000502:physiology; D013577:Syndrome
D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D002118:Calcium