The ratio of ADP- to ATP-ectonucleotidase activity is reduced in patients with coronary artery disease.
BACKGROUND
CD39 (NTPDase1), an endothelial cell membrane glycoprotein, is the predominant ATP diphosphohydrolase (ATPDase) in vascular endothelium. It hydrolyses both triphosphonucleosides and diphosphonucleosides at comparable rates, thus terminating platelet aggregation and recruitment responses to ADP and other platelet agonists. This occurs even when nitric oxide (NO) formation and prostacyclin production are inhibited. Thus, CD39 represents the main control system for platelet reactivity. Reduced or deficient local ecto-nucleotidase activity may predispose to development of vascular disease. Based on data in animal models and in vitro, CD39 constitutes a new therapeutic modality for vascular disease with a novel and unique mode of action.


METHODS
Lymphocytes were isolated from 46 patients with angiographically proven coronary artery disease (CAD) as well as from matched healthy control subjects. Ectonucleotidase ADPase and ATPase activities (prototypical for the ATPDase activity of endothelial cells) were measured using established radio-TLC procedures.


CONCLUSIONS
In the patients, a decreased ratio of ADPase to ATPase activities (from 1.26 to 1.04) was observed despite increases in both ADPase and ATPase activities. Coronary artery disease was the only independent predictor of a difference in the ADPase/ATPase activity ratio by multivariate linear regression analysis (P=0.0035). This altered ADPase/ATPase activity ratio in patients may represent a reduction in endogenous defense systems against platelet-driven thrombotic events. These data may identify a population of patients with excessive platelet reactivity in their circulation. Increased generation of prothrombotic ADP in these patients implies a potential benefit from therapeutic intervention with soluble forms of CD39.
El-Omar
Magdi M
MM
Department of Medicine-Cardiology, New York University Medical School, New York, NY, USA.
Islam
Naziba
N
Broekman
M Johan
MJ
Drosopoulos
Joan H F
JH
Roa
Donald C
DC
Lorin
Jeffrey D
JD
Sedlis
Steven P
SP
Olson
Kim E
KE
Pulte
E Dianne
ED
Marcus
Aaron J
AJ
D000251:Adenosine Triphosphatases / Q000032:analysis / Q000378:metabolism*; D000368:Aged; D015703:Antigens, CD / Q000032:analysis / Q000378:metabolism*; D001081:Apyrase / Q000032:analysis / Q000378:metabolism*; D002250:Carbon Radioisotopes; D016022:Case-Control Studies; D002855:Chromatography, Thin Layer; D003324:Coronary Artery Disease / Q000201:enzymology*; D006801:Humans; D008214:Lymphocytes / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012307:Risk Factors
D015703:Antigens, CD; D002250:Carbon Radioisotopes; D000251:Adenosine Triphosphatases; C027201:ectoATPase; D001081:Apyrase; C067869:CD39 antigen